CANCERJOURNALS
1. 1. A case of spontaneous regression of hepatocellular carcinoma with multiple lung metastases
Hiroyuki Kojima, Noboru Tanigawa, Shuji Kariya, Atsushi Komemushi, Yuzo Shomura, SatoshiSawada, Eitatsu Arai, and Yoshiro
Radiation Medicine 2006: Vol.24 No.2, pp 139-142
http://www.springerlink.com/content/v24352810r532032/
Abstract
Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. We present therein the case of a patient with
hepatocellular carcinoma with multiple lung metastases in whom malignancy spontaneously regressed after taking Phellinus linteus
Mycelium. A 79-year-old man consulted our hospital complaining of epigastric discomfort. Abdominal MRI and CT revealed a 3 cm
diameter tumor in the liver, and chest CT showed numerous nodular lesions. The levels of alpha-fetoprotein (AFP) and protein induced
by VitaminK deficiency or antagonist-II (PIVKA-II) were very high. We diagnosed HCC with multiple lung metastases, and no therapy
was performed. Independently he took exact from Phellinus linteus Mycelium for one month, and 6 months later the tumors appeared to
be in complete regression. The mechanism underlying this intriguing phenomenon remains unknown.
2. A medicinal mushroom: Phellinus linteus
Tongbo Zhu, Sung-Hoon Kim and Chang-Yan Chen
Current Medicinal Chemistry, 2008, 15, 1330-1335
Harvard Medical School
http://www.ingentaconnect.com/content/ben/cmc/2008/00000015/00000013/art00009
Abstract
Phellinus linteus (Berkeley & M. A. Curtis) Teng (PL) is a medicinal mushroom that has been practiced in oriental countries for centuries
to prevent ailments as diverse as gastroenteric dysfunction, diarrhea, haemorrhage and cancers. In an effort to translate the Asian
traditional medicines into western-accepted therapies, scientists have demonstrated that the extracts from fruit-bodies or mycelium of
PL not only stimulate the hormonal and cell-mediated immune function and quench the inflammatory reactions caused by a variety of
stimuli, butalso suppress the tumor growth and metastasis. Mounting evidence from different research groups has shown that PL
induces apoptosis in a host of murine and human carcinomas without causing any measurable toxic effects to their normal
counterparts. Recently, research has been focused on the anti-tumor effect of PL, and in particular, on its ability to enhance some
conventional chemo- therapeutic drugs. These studies suggest PL to be a promising candidate as an alternative anticancer agent or a
synergizer for existing antitumor drugs. Hereinafter, we summarize the present progress in elucidating the mechanisms underlying
the potency of PL and its anti-tumor function.The fractionation and identification of the biologically active components from PLare also
briefly introduced.
3. Acidic polysaccharide from Phellinus linteus inhibits melanoma cell metastasis by blocking cell adhesion and invasion
Sang-Bae Han, Chang Woo Lee, Jong Soon Kang, Yeo Da Yoon, Ki Hoon Lee, Kiho Lee, Song- Kyu Park , Hwan Mook Kim
International Immunopharmacology 2006; 697-702
http://www.sciencedirect.com/science/article/pii/S1567576905002894
Abstract
The acidic polysaccharide (PL) from Phellinus linteus is an immunostimulator that has therapeutic activity against cancers. Here, we
show that PL markedly inhibits melanoma cell metastasis in mice, and report that PL directly inhibits cancer cell adhesion to and
invasion through the extracellular matrix, but that it has no direct effect on cancer cell growth. In addition, we found that PL increased
macrophage NO production. These results suggest that PL has two antimetastatic functions, i.e., it acts as an immunopotentiator and
as a direct inhibitor of cancer cell adhesion.
4. Acidic polysaccharide isolated from Phellinus linteus enhances through the up regulation nitric oxide and tumor necrosis
factor- α from peritoneal macrophages
GYKim, GS Choi, SH Lee, YM Park
Journal of Ethnopharmacology, 95 (1) 69-76, 2004
http://www.sciencedirect.com/science/article/pii/S0378874104003113
Abstract
Medicinal mushrooms are increasingly used to treat a wide variety of disease processes. Aqueous extract from the fruiting body or
mycelia of Phellinus linteus has been reported to produce antitumor and immunomodulatory activities in vivo and in vitro. However, the
mechanisms underlying its tumoricidal effects are poorly understood. The tumoricidal activity of peritoneal macrophages (PM)cultured
with acidic polysaccharide (PL) isolated from Phellinus linteus against B16 melanoma cells was enhanced in a dose-dependent manner;
growth inhibition increased 4-fold with 200 μg/ml of PL. To further characterize the mechanisms of PL, we investigated the effects of
PL onphagocytosis and the release of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and reactive oxygen intermediates (ROI). To
investigate the phagocytosis of PM, the uptake of Dextran (Dex)-FITC between PL-untreated and PL-treated PM was compared. We found
some augment in phagocytosis of PL-treated PM compared untreated group. PL stimulated a dose-dependent increase in NO and TNF-α,
but not in ROI production in PM. We suggested that PL has cytotoxicity against Yac-1 cells through the up-regulation of NO and TNF-
alpha production. Also, PL enhanced the expression of costimulatory molecules, CD80 and CD86, and major histocompatibility complex
(MHC)molecules II in PM. The ability of PL upon the up-regulation of these surface molecules involved in antigen-presenting processes
may, by inference, activate T-cell -mediated immunity against malignant cells in vivo. Taken together, these results suggest that PL
act as an effective immunomodulator and enhances the anti-tumoral activity of PM.
5. Acidic polysaccharide isolated from Phellinus linteus induce phenotypic and functional maturation of murine dendritic cells
Soon-Kew Park, Gi-Young Kim Jae-Young Lim, Jong-Young Kwak, Yoe-Sik Bae, Jae-Dong Lee, Yang-Hyo Oh, Soon-Cheol Ahn and Yeong-Min Park
Biochemical and Biophysical Research Communication 312 (2003) 449-458
http://www.ncbi.nlm.nih.gov/pubmed/14637158
Abstract
Acidic polysaccharides (PL) isolated from Phellinus linteus are known to stimulate the proliferation of T lymphocytes and humoral
immune functions to act as a polyclonal activator of B cells, and to inhibit tumor growth and metastasis. However, little is known about
their immunomodulating effects or the effects of its mechanisms on murine bone marrow (BM)-derived dendritic cells (DC). In this
study, it profoundly increased CD80, CD86, MHC I, and MHCII expression in murine, GM-CSF and IL-4 stimulated, BM-derived myeloid
DC. The ability of unstimulated DC to uptake dextran was higher than that of PL- or LPS-stimulated DC. We analyzed the
concentrationof IL-12 secreted by DC using flow cytometry and ELISA. Untreated DC secreted a low concentration of IL-12,while PL- or
LPS-stimulated DC secreted higher levels of IL-12 than untreated DC. There were no remarkable differences in the concentrations of
IL-12 produced by PL- or LPS-stimulated DC. However, polymyxin B (PB; an LPS inhibitor) effectively inhibited the surface molecules
and IL-12 production induced by LPS, but had no effect on the PL in DC. PL-treated DC were much more potent antigen-presenting
cells in allogeneic immune response than untreated DC. PL treatment not only formed morphologically mature DC but also induced
predominant migration to lymphoid tissues. Moreover, the inhibitors of protein tyrosine kinase (PTK) or protein kinase C (PKC)
significantly blocked the expression of surface molecules and IL-12 production in PL-stimulated DC. Treatment of DC with PL directly
induced PKC activity and phosphorylated PTK. Furthermore, CD11b and/or CD18 partially mediated PL-induced DC maturation.
6. 6. Acidic polysaccharide isolated from Phellinus linteus induces nitric oxide-mediated tumoricidal activity of macrophages through
protein tyrosine kinase and protein kinase
Kim GY Oh YH Park YM
Biochemical Biophys Res Commun 2003 Sep. 309 399-407
Abstract
Mushroom polysaccharides are increasingly being utilized to treat a wide variety of diseases. Aqueous extracts from the Phellinus
linteus been reportedto have anti-tumor and immunomodulatory properties. In particular, acidic polysaccharide (PL) isolated from
P. linteus induced a secretory and cellular macrophage response. However, the exact mechanism by which PL regulates the
macrophage functions remains unclear. PL-treated murine peritoneal macrophage in vitro and in vivo dramatically induced the
production of NO. PL enhanced the lytic death of B16 cell through the production of NO. The precent study examined signal molecules
that may participate in PL- elicited responses by macrophages. The data demonstrated that a protein kinase C (PHC) inhibitor,
staurosporine, and a protein tyrosine kinase (PTK) inhibitor, genistei, inhibitor the tumoricidal activity of macrophages induced by PL.
In addition, these inhibitor blocked the production of NO and the expression of surface molecules in PL-stimulated macrophages.
Furthermore, CD11b2/CD18 possibly mediates PL-induced cell activation. These results suggest that PL stimulates NO production for
tumoricidal activity and induces cell-mediated immunity by increasing surface molecules, and the process may be a mechanism by
which PL produces its therapeutic effects.
7. Administration of extract of mushroom Phellinus linteus induces prostate enlargement with increase in stromal component
inexperimentally developed rat model of benign prostatic hyperplasia
Y.Shibata, B.Kashiwagi,S.Arai, Y.Fukabori, K.Suzuki
Urology 2006, Volume 66, Issue 2, Pages 455-460
http://www.ncbi.nlm.nih.gov/pubmed/16098375
Abstract
Objectives
To clarify the effect of the mushroom extract Phellinus linteus on noncancerous prostate cells using an experimentally developed rat
benign prostatic hyperplasia model. A growing number of people take some natural herbal extracts for maintenance of their health.
Among them extracts of certain mushrooms are believed to have a marked tumoricidal effect but low toxicity for normal tissues, and
they are being drunk widely in Japan and Korea. However, until now, their effect on noncancerous benign prostate growth has not
been examined.
Methods
The mushroom extract was administered daily for 5 weeks to experimentally developed benign prostatic hyperplasia rats. Prostate
organ weight, histologic composition, and gene expression levels of sex hormone receptors, transforming growth factor-beta, vascular
endothelial growth factor, and endothelial nitricoxide synthase were examined.
Results
Prostate weight increased significantly by 37% owing to treatment with the mushroom extract (P <0.05). In particular, the stromal
component of the prostate increased significantly by 80% (P <0.05). A suppression of transforming growth factor-beta1expression by
56% was observed with the mushroom extract treatment (P <0.05).
Conclusions
We found that the mushroom extract enlarged the prostate. The effect was suggested to be on the prostate stroma, which may be
involved in transforming growth factor-beta1regulation. Administration of mushroom extract shouldbe considered carefully by those
with an enlarged prostate.
8. 8. Alleviation of experimental septic shock in mice by acidic polysaccharide isolated from the medicinal mushroom Phellinus
linteus
Kim GY, Roh SI, Park SK, Ahn SC, Oh YH, Lee JD, Park YM
Biol Pharm Bull 2003 Oct; 26: 1418-23
Abstract
This study reports that acidic polysaccharide (PL) isolated from Phellinus linteus alleviated the septic shock induced by high dose
lipopolysaccharide(LPS) injection in mice. To examine the origin of this effect, we investigated cytokine production in serum and the
expression of MHC II in B cells and macrophages in areas of inflammation. Pretreatment with PL 24 h before LPS administration
resulted in a significant inhibition of up to 68% of circulating tumor necrosis factor(TNF)-alpha, a moderate reduction of 45% of
interleukin(IL)-12 and 23% of IL-1beta, but no significant reduction in IL-6. In addition, the expression of MHC II in B cells and
macrophage was examined. Our results show that LPS-stimulated cytokine release and the level of MHC II can be modulated by in vivo
administration of soluble PL in mice. The decrease of IL-1beta, IL-12 and TNF-alpha in sera and the down-modulation of MHC II during
septic shock may contribute to the survival of mice by PL. Administration of PL in vivo decreases IL-2, IFN-gamma and TNF-alpha
production in splenocytes and enhances spontaneous cell apoptosis in macrophages and lymphocytes stimulated with LPS in vitro.
Thus, part of the anti-inflammatory effects of PL treatment in vivo may result from the enhanced apoptosis of a portion of the activated
macrophages and lymphocytes. The ability of PL to significantly reduce the TNF-alpha production indicates the potential of the
polysaccharides in possible therapeutic strategies that are based on down-regulation of TNF-alpha.
9. An antioxidant hispidin from the mycelia cultures of Phellinus linteus
In-Hye Park, Shin-Kyo Ching, Kyung-Bok Lee,Yung-Choon Yoo, Suk-Kyung Kim, Geum-Soog Kim and Kyung-Sik Song
Arch Pharm Res Vol 27, No 6, 615-618, 2004
www.springerlink.com/content/992r5w640237p0w2/
Abstract
In the course of screening for reactive oxygen species scavengers from natural products, an antioxidant was isolated from the mycelia
culture broth of Phellinus linteus and identified as hispidin.The hispidin content was reached its maximum level at 12 days after onset
of inoculation. About 2.5 mg/mL of hispidin was produced by P.linteusin a yeast-malt medium (pH 5.8, 25°c). Hispidin inhibited 22.6
and 56.8% of the super oxide anion radical, 79.4 and 95.3% of the hydroxyl radical, and 28.1 and 85.5% of the DPPH radical at 0.1 and
1.0 mM, respectively. The positive control α-tocopherol scavenged 25.6 and 60.3%, 74.6 and 96.3% and 32.7 and 77.5% of each radical,
respectively at the same concentrations. However, hispidin showed no significant activity on the hydrogen peroxide radical.
10. Antagonizing TGF-beta induced liver fibrosis by a retinoic acid derivative through regulation of ROS and calcium influx
Biochem Biophys Res Commun .2008 Jan 18;365(3):484-9
http://www.ncbi.nlm.nih.gov/pubmed/17997979
Abstract
Transforming growth factor-beta1(TGF-β1) mediates the regulation of extracellular matrix via reactive oxygen species (ROS) and
calciuminflux, both are activators of hepatic stellate cells(HSC) which play a critical role in hepatic fibrogenesis. Hence one can use
ROS assayas the main screening tool for molecules that might antagonize theprocess of liver fibrosis. A retinoic acid derivative
isolated from the mycelium of Phellinus linteusthat down-regulates ROS generation andcalcium influx in HSC-T6 cells was thus
obtained in our screening process. The retinoic acid derivative also reverses an early liver fibrosis, as assayed by liver contents of
hydroxyproline, α-smooth muscleactin (α-SMA), and collagen1A2, in an early liver fibrosis model we established previously where an
inducible expression vector containing a TGF-β gene was hydrodynamically transferred into a testing animal. Retinoic acid derivative
thus acts both in vitro and in vivo to prevent liver fibrosis at an early phase.
11. Anti-angiogenic, antioxidant and xanthine oxidase inhibition activities of the mushroom Phellinus linteus
YunSeon Song, Sun-Hyoung Kim, Jae-Hoon Sa, Changbae Jin, Chang-Jin Lim and Eun-Hee Park Journal of Ethnopharmacology 88 (2003) 113-116
http://www.ncbi.nlm.nih.gov/pubmed/12902060
Abstract
Fruitingbodies of Phellinus linteus were extracted with 70% ethanol at room temperature. The Phellinus linteusextract (PL) showed
strong anti-angiogenic activity, which was detected using the chick embryochorioallantoic membrane (CAM) assay. The in vitro
antioxidant activities of PL were evaluated using two different bioassays. PL was comparable to Vitamin C in scavenging the stable free
radical 1,1-diphenyl-2-picrylhyrazyl (DPPH). It also inhibited lipid peroxidation (LPO) in a concentration-dependent manner.
These results suggest that antioxidant and anti-angiogenic activities of Phellinus linteuswould be partly responsible for its anti-tumor
effect.
12. Anti-cancer activities of ginseng extract fermented with Phellinus linteus
Jong-JinLee, Ho-Kyun Kwon, In-Ho Jung, Yong-Baik Cho, Kyu-Joong Kim and Jong-Lae Kim
TheKorean Society of Mycology, Mycobiology 37(1): 21-27 (2009)
http://www.mycobiology.or.kr/Upload/files/MYCOBIOLOGY/37(1)%2021-27.pdf
Abstract
In the present study, the anti-cancer effects if ginseng fermented with Phellinus linteus(GFPL) extract were examined through in vitro
and in vivo assays.GFPL was produced by co-cultivating ginseng and Phellinus linteus together. Ginsenoside Rg3,Rh1 and Rh2 are
important mediators ofanti-angiogenesis and their levels in GFPL were enriched 24,19 and 16 times,respectively, more than that of
ginseng itself through the fermentation, GFPL exhibited distinct anti-cancer effects, including growth inhibition of thehuman lung
carcinoma cell line A549, and promotion of immune activation by stimulating nitric oxide (NO) production in Raw 264.7 cells. Further
evidence supporting anti-cancer effects of GFPL was its significant prolongment of the survival of B16F10 cancer cell-implanted mice.
These results suggest that the GFPL may be a candidate for cancer prevention and treatment through immune activation and anti-
angiogenic effects by enriching Rg3, Rh1 and Rh2.
13. Antimutagenicity and induction of anticarcinogenic phase II enzymes by basidiomycetes
ShonYH, Nam KS
J Ethnopharmacol 2001 Sep; 77: 103-9
http://www.sciencedirect.com/science/article/pii/S03788741010027689
Abstract
Extracts form Phellinus linteus, Phellinus igniarius, and Agrocybe cylindracea have been tested for their antimutagenic properties
against direct-acting mutagens[4-nitro-o-phenylenediamine (NPD) and sodium azide (NaN(3))] and indirect-acting mutagens
[2 aminofluorene (2-AF) and benzo [a] pyrene (B[a]P)],using the Salmonella typhimurium tester strains TA 98 and TA 100. In addition,
the chemo preventive potentials of these extracts to induce NAD (P) H: quinonoxidoreductase (QR) and glutathione S-transferase (GST)
activities and glutathione(GSH) level extracts from the filtrate of the cultured broth of P. linteus, polysaccharide extracts from the
cultured broth (PI I) and mycelia(PI II) and water extract of fruiting bodies (PI II) of P. igniarius, and polysaccharide extracts from the
cultured (AC I) and mycelia (AC II) of A. cylidracea showed inhibitory effects on the mutagenic activities induced by the direct-
acting mutagens, NPE and NaN (3),and the indirect-acting mutagens, 2-AF and B[a]P. QR was induced withPI I,PI II,AC I, and AC II, and
GST activity induced with PL I,PL II,PI I,PIII,PI III and AC I in murine Hepa1c1c7 cell culture. In addition, PL I, PLII,PI I,PI II,PI III and
AC II increased glutathione level. These results suggest that P. lintues, P. igniarius, and A. cylindracea have antimutagenic activities
and may play a role in the prevention of cancer by inducing QR and GST activities and increasing GSH level.
14. Antimutagenicity of Phellinus linteus in Salmonella typhimurium
ShonYun-Hee, Lee Jae-Sung, Lee Hang-Woo, Kim Joong-Wan, Lim Jong-Kook, Kim Cheorl-Ho, Nam Kyung-Soo
The Journal of Microbiology, 37(3),136-140, 1999
http://www.msk.or.kr/jsp/view_old_journalD.jsp?paperSeq=1644
Abstract
The mutagenicities and antimutagenicities of butanol(PL I) and water (PL II) extracts from the filtrate of the cultured broth of Phellinus
linteus were examined using the Ames/Salmonella test. No mutagenic activityof PL I and PL II was found in Salmonella typhimurium
strains TA98 and TA100, either with or without S9 activation. In contrast, PL I and PL II showed inhibitory effects on the mutagenic
activities induced by the directly-actingmutagens, 4-nitro-o-phenylenediamine (NPD) using the tester strain TA98 andsodium azide
(NaN₃) using the tester strain TA 100 in the absence of S9 mix. PLI and PL II also showed inhibitory effects on the mutagenicities of
the indirectly-acting mutagens,2-aminofluorene (2-AF) using the tester strain TA98 and benzo[a]pyrene (B[a]P)using the tester strain
TA 100 in the presence of S9. These results suggestthat P. linteus has an antimutagenic activity and may play a role in the
prevention of cancer.
15. Antioxidant polyphenols from themycelial culture of the medicinal fungi Inonotus xeranticus and Phellinus linteus
J.-Y. Jung, I.-K. Lee, S.-J. Seok, H.-J. Lee, Y.-H. Kim and B.-S. Yun
Journal of Applied Microbiology 104 (2008) 1824–1832
http://www.ncbi.nlm.nih.gov/pubmed/18266700
Abstract
Aims: The medicinal fungi Inonotus xeranticus and Phellinus linteus in the family Hymenochaetaceae have been used as traditional
medicines for the treatment of various diseases. However, the compound responsible for the antioxidant activity is still unknown.
Therefore, this study was conducted to characterize the antioxidant substances present in cultured broths made from these fungi.
Methods and Results: Antioxidant fractions of the cultured broths obtained from I. xeranticus and P.linteus were analyzed using
reversed-phase HPLC, which revealed several peaks that exhibited a potent free radical scavenging activity. To identify these
antioxidant peaks, an I. xeranticus strain was mass cultured, and the cultured broth was separated using antioxidant activity guided
fractionation. Four major active substances were purified and identified as hispidin and its dimers, 3,14￠-bihispidinyl, hypholomine B,
and 1,1-distyrylpyrylethan based on spectroscopic analyses. All compounds exhibiteda significant scavenging activity against these
radical species in a concentration dependent manner.
Conclusions:Antioxidant substances found in the cultured broths of the medicinal fungi I.xeranticus and P. linteus were identified as
hispidin and its dimers, 3,14￠-bihispidinyl, hypholomine B, and 1,1-distyrylpyrylethan.
Significance and Impact of the Study: Polyphenol antioxidants were isolated from thec ultured broth of the medicinal fungi I. xeranticus
and P. linteus and identified based on extensive spectroscopic analyses. These compounds exhibited a strong antioxidant activity.
16. Antitumor effects and immunomodulating activities of PL extract in a CT-26 cell-injected colon cancer mouse model
Byung-Keun Yang, Seung-Lark Hwang, Ik-Jim Yun,Eun-Ju Do, Won-Ha Lee, Young-Mi Jung,Sung-Chang Hong and Dong-Chan Park
The Korean Society of Mycology, Mycobiology37(2):128-132 (2009)
www.mycobiology.or.kr/Upload/files/.../37(2)%20128-132.pdf
Abstract
The antitumor effects of Phellinus linteus extract (Keumsa Linteusan) were investigated in a CT-26 cell-injected colon cancer
mouse model.When administered orally (250~1,000 mg/kg body weight), Keumsa Linteusan significantly inhibited the growth of solid
colon cancer. The highest dose washighly effective, reducing tumor formation by 26% compared with the control group. The
anticomplementary activity of Keumsa Linteusan increased in adose-dependent manner. Lysosomal enzyme activity of macrophages
was increased by 2-fold (100 µg/ml) compared with the control group. Keumsa linteusan can beregarded as a patent enhancer of the
innate immune response, and can be considered as a very promising candidate for antitumor action.
17. Anti-tumor activity of the rruitbody extract of Basidiomycete, Phellinus linteus
Jong-Soon Lim, Seung-Hyung Kim, Jin-Seo Park,Jeong-Youl Choi , Seong Joo Park, and Kwang-Soo Shin
The Journal of Microbiology, 39(2), 121-125, 2001
www.msk.or.kr/jsp/downloadPDF1.jsp?fileName=392-5.pdf
Abstract
Methanol extract prepared from the fruitbody of Phellinus linteus (EPL) showed anti-tumor and immuno-stimulating activities. The
invasion activity of B16-F10 melanoma cells through a reconstituted basement membrane to the collagen-coated lower surface of the
filters was inhibited about 67% by EPL (100 ug/ml). Also, EPL inhibited the expression of the mRNAfor MMP-2 and MMP-9. In vivo
treatment of C57BL/6 mice (150 mg/kg) with EPL for14 days, the pulmonary colonization was found to be inhibited about 75%. Using
reverse transcription polymerase chain reaction (RT-PCR) analysis, we found that cytokine IL-12 and INF-[gamma] genes were induced
by EPL. Furthermore, EPL stimulated the proliferation of CD4^+ (33.5%) and CD8^+ (17.7%) in mouse splenocytes.
18. Antitumor polysaccharides from some polyporaceae, Ganoderma applanatum (Pers.) Pat and Phellinus linteus (Berk. et Curt
Aoshima
Sasaki T, Arai Y, Ikekawa T, Chihara G, Fukuoka F
Chem Pharm Bull (Tokyo). 1971 Apr;19(4):821-6
Abstract
Antitumor polysaccharide preparations G-Z and P-Z were fractionated from the water soluble extracts of Ganoderma applanatum (PERS.)
PAT and Phellinus linteus (BERK, et CURT)AOSHIMA, basidiomycetes of Polyporaceae, respectively by fractional precipitation with
ethanol and cetyltrimethylammonium hydroxide. The structure of G-Z and P-Z consist of β-(1-3), (1-4) linked D-glucose residue and
β-(1-3) linked D-glucose residue, respectively. These polysaccharide preparations have marked antitumor activity against transplanted
sarcoma 180 in mice, and a complete regression of tumors was observed in more than half of animals with no sign of toxicity. Some
derivations of P-Z were synthesized and their antitumor effect were also examined.
19. Cambodian Phellinus linteus inhibits experimental metastasis of melanoma cells in mice via regulation of urokinase type
plasminogen activator
HJLee, HJ Lee, ES Lim, KS Ahn, BS Shim, HM Kim, SJ Gong, DK Kim, SH Kim
Biol.Pharm. Bull., Vol. 28, 27-31 (2005)
http://www.jstage.jst.go.jp/article/bpb/28/1/27/_pdf
Abstract
Phellinus linteus (PL) is a fungus mainly found in tropical America, Africa and Asian countries including Korea, Japan and China. PL
has been traditionally used for the treatment ofarthritis, liver damage and cancer. However, little was known on the biologicalactivity
and characterization of Phellinus species in Cambodia. Thus, inthe present study, the anti-metastatic mechanism of aqueous extract
of Cambodian Phellinus linteus (CPL) was evaluated. Cambodian mushroom was identified as a Phellinus species with 99% homology of
Phellinus linteus by DNA sequence analysis and comparison by the National Center for Biotechnology Information. CPL did not exhibit
any significant cytotoxicity against B16BL6 cells, invasive melanoma cells at 1 mg/ml. However, CPL inhibited platelet aggregation
induced by B16BL6 cells and also disrupted the adhesion to gelatin and invasion of B16BL6 cells in a concentration dependent
manner. Similarly, CPL dose-dependently inhibited the pulmonary metastatic colonies in C57BL/6 mice intravenously injected by
B16BL6 cells up to 55.5% ata dose of 50 mg/kg compared with untreated control. CPL also down-regulated the expression of urokinase
type plasminogen activator (uPA), one of key proteins associated with invasion and metastasis of tumor cells in a concentration
dependent fashion, while CPL didn't significantly affect the expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of
metalloproteinase 2(TIMP-2) by reverse transcriptase–polymerase chain reaction (RT-PCR). Taken together, these findings indicate
that Cambodian Phellinus linteus may inhibit metastasis at least partly via regulation of uPA associated with tumor cell induced platelet
aggregation (TCIPA) and also suggest a further study for isolation of active ingredients and the involvement of adhesion molecule
signaling pathway.
20. 20. Dramatic remission of hormone refractory prostate cancer achieved with extract of the mushroom, Phellinus linteus
ShibataY,Kurita S, Okugi H, Yamanaka H
Urol Int 2004; 73:188-90
http://content.karger.com/ProdukteDB/produkte.asp?Doi=79704
Abstract
At present, there is no distinctly effective treatment for hormone refractory prostate cancer. We describe a hormone refractory prostate
cancer patient with rapidly progressive bone metastasis who showed dramatic response to intake of an extract from the mushroom,
Phellinus linteus.
21. Extracts of medicinal mushrooms Agaricus bisporus and Phellinus linteus induce proapoptotic effects in the human leukemia
cell line K562
Alla V. Shnyreva,Wei Song, & Leo J. L. D. Van Griensven
International Journal of Medicinal Mushrooms, 12(2):167-175(2010)
http://library.wur.nl/WebQuery/wurpubs/392845
Abstract
We have studied the effects of Agaricus bisporus and Phellinus linteus ethanol extracts on transcriptional regulation of genes involved in
cytokine release and apoptosis in the human leukemia cell line K562. In particular, we applied quantitative real-time PCR (Q-PCR)
assays to monitor alterations of gene expression for the following genes:Bcl-2, Casp-9, NF-κB, TNF-α, IFN-γ, and IL-10. We found
stronger proapoptotic activity for the Ph. linteus alcohol extract on K562 cells than for the A. bisporus extract:4.4- and 2.2-fold increase of
Bcl-2 and Casp-9 transcripts. Mushroom alcohol extracts are suggested to exert their effects on tumor cells via the induction of
apoptosis. K562 leukemia cells were shown to be most responsive to the transcriptional induction of tumor necrosis factor TNF-α when
stimulated with IFN-γ and then treated with Ph. linteus alcohol extract: up to a 4.5-fold increase. Treatment of K562 cells with
A.bisporus extract promoted transcription of the cytokine gene IL-10.
22. Extracts of Phellinus linteus grown on germinated brown rice suppress liver damage induced by carbon tetrachloride in rats
Tae Il Jeon, Seong-Gu Hwang, Beong Ou Lim & Dong Ki Park
Biotechnology Letters 25: 2093-2096, 2003
http://www.springerlink.com/content/x2063024rk8q2t78/
Abstract
Extracts of Phellinus linteus(EPB),grown on germinated brown rice, protected rats from liver injury induced by carbon tetrachloride(CCI4).
Peroxidation products in the liver were decreased to 10% by EPB. Catalase and superoxide dismutase activities were significantly
decreased to 55% and 39% by CCI4 administration, but EPB blocked this effect, resulting in enzyme activities at control levels.
Expression of cytochrome P4502E1(CYP2E1) protein was significantly decreased to 88% in CCI4-treated rats but remained at control
levels when EPB was also administered. EPB did not affect the altered fatty acid composition induced by CCI4 .The hepatoprotective
effect of EPB may be mediatedby EPB’s prevention of CCI4-induced CYP2E1 degradation.
23. Fractionation and anti-tumor activity of the mycelia of liquid-cultured Phellinus linteus
Nakamura T. Matsugo S. Uzuka Y. Matsuo S. Kawagishi H.
Biosci Biotechnol Biochem 2004 Apr;68;868-72
http://jstage.jst.go.jp/article/bbb/68/4/868/pdf
Abstract
All the fractions of Phellinus linteus mycelia showed anti-tumor activity toward solid tumors planted in mice. The highest anti-tumor
activity of 81.2%was observed in the protein–glucan complex obtained by precipitating the 24%NaOH extract at pH 6.0. This protein–
glucan complex consisted of 39.3% polysaccharide and 49.4% protein. Its 13C- and 1H-NMRdata showed that the main glucan part of the
complex was simple alpha-1, complex was simple alpha-1,3-glucan chains.
24. Hispolon from Phellinus linteushas antiproliferative effects via MDM2-recruited ERK1/2 activity in breast and bladder cancer
cells
Te-Ling Lu, Guan-Jhong Huang, Te-Jung Lu, Jin-Bin Wu, Chieh-Hsi Wu, Tung-Chuan Yang, Akira Iizuka and Yuh-Fung Chen
Food and Chemical Toxicology Volume 47, Issue 8, , August 2009, Pages 2013-2021
http://www.ncbi.nlm.nih.gov/pubmed/19477214
Abstract
The MDM2 proto-oncogene is over expressed in many human tumors. Although MDM2 inhibits tumor-suppressor function of p53,
there exists a p53-independent role for MDM2 in tumorigenesis.Therefore, downregulation of MDM2 has been considered an attractive
therapeutic strategy. Hispolon extracted from Phellinus species was found to induce epidermoid and gastric cancer cell apoptosis.
However, the mechanisms are not fully understood. Herein, we report our findings that hispolon inhibited breast and bladder cancer
cell growth, regardless of p53 status. Furthermore, p21WAF1, a cyclin-dependent kinase inhibitor, was elevated in hispolon-treated cells.
MDM2, a negative regulator of p21WAF1, was ubiquitinated and degraded after hispolon treatment. We also found that activated ERK1/2
(extracellular signal-regulated kinase1/2) was recruited to MDM2 and involved in mediating MDM2 ubiquitination. Based on this
finding, we investigated whether the sensitivity of cells to hispolon was related to ERK1/2 activity. The results indicated that cells with
higher ERK1/2 activity were more sensitive to hispolon. In addition, hispolon-induced caspase-7 cleavage was inhibited by the ERK1/2
inhibitor, U0126. In conclusion, hispolon ubiquitinates and downregulates MDM2 via MDM2-recruited activated ERK1/2. Therefore,
hispolon may be a potential anti-tumor agent in breast and bladder cancers.
25. Hispolon induces apoptosis in human gastric cancer cells through a ROS-mediated mitochondrial pathway
Chen W, Zhao Z, Li L, Wu B, Chen SF, Zhou H, Wanf Y, Li YQ
Free Radical Biology & Medicine 45 (2008) 60-72
http://www.sciencedirect.com/science/article/pii/S089158490800155X
Abstract
Severe side effects and complications such as gastrointestinal and hematological toxicities because of current anticancer drugs are
major problems in theclinical management of gastric cancer, which highlights the urgent need fornovel effective and less toxic
therapeutic approaches. Hispolon, an active polyphenol compound, is known to possess potent antineoplastic and antiviral properties.
In this study, we investigated the efficacy of hispolon in human gastric cancer cells and explored the cell death mechanism. Hispolon
induced ROS-mediated apoptosis in gastric cancer cells and was more toxic toward gastric cancer cells than toward normal gastric
cells, suggesting greater susceptibility of the malignant cells. The mechanism of hispolon-induced apoptosis was that hispolon
abrogated the glutathione antioxidant system and caused massive ROS accumulation in gastric cancer cells. Excessive ROS caused
oxidative damage to the mitochondrial membranes and impaired the membrane integrity, leading to cytochrome c release, caspase
activation, an apoptosis. Furthermore, hispolon potentiated the cytotoxicity of chemotherapeutic agents used in the clinical
management of gastriccancer. These results suggest that hispolon could be useful for the treatment of gastric cancer either as a
single agent or in combination with other anticancer agents.
26. Induction of apoptotic cell death by mycelium extracts of Phellinus linteus in human neuroblastoma cells
Choi YH, Huh MK, Ryu CH, Choi BT, Jeong YK
Int J Mol Med. 2004 Aug; 14(2):227-32
http://www.ncbi.nlm.nih.gov/pubmed/15254770
Abstract
Phellinus linteus is a well-known Oriental medicinal fungus that has various biological activities, including immunomodulatory and anti-tumor activities, the mechanisms of which are poorly understood. In the present study, we investigated the effects of mycelium
extract of P. linteus (MEPL) on the growth of human neuroblastoma SK-N-MC cells. Upon treatment withMEPL, a concentration-
dependent inhibition of cell proliferation was observed and cells developed many of the hallmark features of apoptosis, including
condensation of chromatin and an increase in the sub-G1 population. The anti-proliferative and apoptotic effects of MEPL were
associated with a marked induction of the Bax and cyclin-dependent kinase inhibitor p21. Western blotting and in vitro caspase-3
activity assay demonstrated that the processing/activation of caspases accompanies the generation of MEPL-mediating apoptotic cell
death. In addition, the proteolytic cleavage of specific target proteins such as poly (ADP-ribose) polymerase and beta-catenin were
observed.Taken together, the present results suggest that apoptotic signals evoked by MEPL in human neuroblastoma SK-N-MC cells
may converge caspase-3 activation through an up-regulation of Bax rather than a down-regulation of Bcl-2
27. Inhibition ofcytochrome P450 isozymes in rat liver microsomes by polysaccharides derived from Phellinus linteus
Yun-Hee Shon and Kyung-Soo Nam
Biotechnology Letters 25; 167-172: 2003
http://www.springerlink.com/content/tj10431576n64wtt/
Abstract
Polysaccharides (0.5, 1 and 3 mg ml–1) from cultured broth and mycelia of Phellinus linteus inhibited cytochrome P450 (CYP) 1A1, CYP
1A2, CYP 2B1, and CYP 2E1activities in rat liver microsomes. The polysaccharides from the broth of Phellinus linteus grown with 5%
(v/v) mulberry extract had highest inhibitory potency for CYP 1A1, 1A2 and 2B1 activities. The most potent inhibitor of CYP 2E1activity
was the polysaccharides from the broth of Phellinus linteus grown with 10% (v/v) mulberry extract.
28. 28. Inhibition of IgE-dependent mouse triphasic cutaneous reaction by a boiling water fractionseparated from mycelium of
Phellinus linteus
Naoki Inagaki, Tomonori Shibata, Tomokazu Itoh, Tomohiro Suzuki, Hiroyuki Tanaka, Tomoyuki Nakamura, Yukihito Akiyama, Hirokazu Kawagishi
and Hiroichi Nagai
Oxford Journals 2005: Vol.2 No.3, 369-374
Abstract
Phellinus linteus, a mushroom, contains constituents that exhibit potent antitumor effects through activating immune cells. Recently,
anti-inflammatory and anti-allergic properties of P. linteus extracts have also been implicated. In the present study, therefore, we
separated the constituents of mycelium of P. linteus into five fractions—chloroform-soluble (CF), ethyl acetate-soluble (EA), methanol-
soluble (AE), water-soluble (WA) and boiling water-soluble (BW) fractions-and examined their suppressive effects on the IgE-dependent
mouse triphasic cutaneous reaction. The triphasic reaction was induced in the ear of BALB/c mice passively sensitized with anti-
dinitrophenol IgE by painting with 2,4-dinitrofluorobenzene 24 h later. Ear swelling appeared triphasically with peak responses at 1 h,
24 h and 8 days after the challenge. ME, WA and BW given orally at a dose of 100 mg kg–1 significantly inhibited the first and second
phase ear swelling, and BW also inhibited the third phase response. CF only inhibited the second phase. The inhibition by BW was the
most potent and almost dose dependent at doses of 30–300 mg kg–1. BW also inhibited vascular permeability increase caused by
passive cutaneous anaphylaxis anti histamine, and ear swelling caused by tumor necrosis factor-α. In contrast, BW apparently
potentiated the production of interleukin-4 and interferon-γ from anti-CD3-stimulated mouse splenocytes. These results indicate that
BW derived from mycelium of P. linteus contains some constituents with anti-allergic as well as immunopotentiating properties.
29. Inhibitory effect of oral intake of natural Phellinus linteus fruit body on growth and pulmonary metastasis of B16/BL6 melanoma
Takamasa Ohno, Yurika Takahashi, Hiroki Tanabe, Hideki Hirayama, Hajime Mizukami, Yukio Ogihara and Makoto Inoue
Journal of Natural Medicines 2007 Oct:438-442
http://www.springerlink.com/content/r707525163w44137/
Abstract
In the present study, the immunotherapeutic activity of oral intake of natural Phellinus linteusfruit body (nPF) against growth and
pulmonary metastasis of injected B16/BL6melanoma cells has been examined. The nPF powder was orally administered to B16/BL6
bearing mice, a model for the pulmonary metastasis of melanoma, at doses of 83, 415 and 2,075 mg/kg day in their diet. The dietary
intake of nPF powder significantly prolonged the survival time of theB16/BL6-bearing mice. Furthermore, ingestion of nPF dose-
dependently enhanced NO production by macrophages prepared from the tumor-bearing, nPF-treatedanimals. Simultaneously, nPF did
not induce direct cytotoxicity against B16/BL6. These results suggest that the oral intake of nPF powder may be useful in
immunochemotherapy for cancer because of its life prolongation through theinhibitory effect on growth and metastasis of cancer.
30. Medicinal mushroom as a source of antitumor and immunomodulating polysaccharides
S.P.Wasser
Applied Microbiology and Biotechnology (2002) 60:258-274
http://www.cray.su/wasser_polysaccharide.pdf
Abstract
The number of mushrooms on Earth is estimated at 140,000, yet may be only 10% (approximately14,000 named species) are known.
Mushrooms comprise a vast and yet largely untapped source of powerful new pharmaceuticalproducts. In particular, and most
importantly for modern medicine, they represent an unlimited source of polysaccharides with antitumor and immunostimulating
properties. Many, if not all, Basidiomycetes mushrooms contain biologically active polysaccharides in fruit bodies, cultured mycelium,
culture broth. Data on mushroom polysaccharides have been collected from 651species and 7 infraspecific taxa from 182 genera of
higher Hetero- and Homobasidiomycetes. These polysaccharides are of different chemical composition, with most belonging to the
group of #-glucans; these have #-(1M3)linkages in the main chain of the glucan and additional #-(1M6) branch pointsthat are needed
for their antitumor action. High molecular weight glucans appear to be more effective than those of low molecular weight. Chemical
modificationis often carried out to improve the antitumor activity of polysaccharides and their clinical qualities (mostly water
solubility). The main procedures used for chemical improvement are: Smith degradation (oxydo-reducto-hydrolysis), formolysis, and
carboxymethylation. Most of the clinical evidence for antitumor activity comes from the commercial polysaccharides lentinan,
PSK (krestin), and schizophyllan, but polysaccharides of some other promising medicinal mushroom species also show good results.
Their activity is especially beneficial in clinics when used in conjunction with chemotherapy. Mushroom polysaccharides prevent
oncogenesis, show direct antitumor activity against various allogeneicand syngeneic tumors, and prevent tumor metastasis.
Polysaccharides from mushrooms do not attack cancer cells directly, but produce their antitumoreffects by activating different immune
responses in the host. The antitumor action of polysaccharides requires an intact T-cell component; their activity is mediated through
a thymus-dependent immune mechanism. Practical applicationis dependent not only on biological properties, but also on
biotechnological availability. The present review analyzes the pecularities of polysaccharides derived from fruiting bodies and cultured
mycelium (the two main methods of biotechnological production today) in selected examples of medicinal mushrooms. (PL is
mentioned in p.271)
31. Medicinal mushroom Phellinus linteus as an alternative cancer therapy
Daniel Sliva
Experimentaland Therapeutic Medicine May-June 2010 Volume 1 Number 3 Pages: 407-411
http://www.spandidos-publications.com/etm/1/3/407
Abstract
Alternative cancer treatment with nutritional/dietary supplements containing a wide variety ofherbal products is on the rise in
Western countries. Recent epidemiological studies have suggested that mushrooms may prevent against different types ofcancers.
Phellinus linteus is a well-known Oriental medicinal fungus with a variety of biological activities, including immunomodulatory or
direct antitumor activities. The activity of P. linteus and its extracts is associated with the presence of polysaccharides, their
peptide/protein complexes and otherlow molecular weight complexes. Polysaccharide fractions isolated from P.linteus were found to be
related to the increased activity of immune cells such as the production of cytokines by macrophages and B-cells or the increased
cytotoxic activity of natural killer cells. Moreover, P. linteus was found tomodulate the expression or activity of various genes involved
in cell proliferation, apoptosis, angiogenesis, invasive behavior and chemoprevention.Finally, P. linteus extracts demonstrated tumor
regression in three independentcase reports, suggesting that an extract from P. linteus or a dietarysupplement based on the extract
from P. linteus may have potential use for the alternative treatment of cancer.
32. Modulation of lung cancer growth arrest and apoptosis by Phellinus linteus
Jinjin Guo , Tongbo Zhu , Lea Ann Collins , Zhi-Xiong J. Xiao , Sung-Hoon Kim , Chang-Yan Chen
Molecular Carcinogenesis 2006, 46 (2), 144-54
http://onlinelibrary.wiley.com/doi/10.1002/mc.20275/full
Abstract
The Phellinus linteus (PL) mushroom has been shown to possess anti-tumorproperties. Through influencing lymphocytes, PL indirectly
augments the host's immune system against cancer cells. PL has also been demonstrated to reduce tumor proliferation. However, the
mechanisms of PL against malignant growth have not yet been fully explored. In this study, we report that PL mediates the following
two activities in mouse and human lung cancer cells: cell-cycle arrest at a low concentration of PL and apoptosis in response to a high
dose of PL. After exposure to a low dose of PL, G(1) growth arrest occurred in the lungcancer cells. The negative growth control mediated
by PL is evidenced by the decrease of the activities of cyclin-dependent kinases CDK2, 4, and 6. Incontrast, at high doses, PL-induced
lung cancer cells to undergo apoptosis in a dose-dependent fashion. This was evidenced by DNA fragmentation, caspase activation, and
loss of clonognecity in the lung cancer cells, all of which were lacking in the lung cancer cells treated with low concentrations of of PL
as wellas the normal mouse lung epithelial cells exposed to either low or high concentrations of PL. The addition of the caspase
inhibitor Z-VADfmk completely suppressed PL-induced apoptosis. Furthermore, the low dose of PL was able to synergize with
doxorubicinto induce apoptosis in the lung cancer cells. Thus,our findings suggest that PL regulates two responses in the lung cancer
cells:cell-cycle arrest and apoptosis.
33. Mycelial culture of Phellinus linteus protects primary cultured rat hepatocytes against hepatotoxins
S.H. Kim, H.S. Lee, S. Lee, J. Cho, K. Ze, J. Sung and Y.C.Kim
Journal of Ethnopharmacology Volume 95, Issues 2-3, December 2004, Page 367-372
http://www.sciencedirect.com/science/article/pii/S0378874104003757
Abstract
Hepatoprotective activity of Phellinus linteus was studied using H2O2- or galactosamine-injured primarycultures of rat hepatocytes as
screening systems. The methanolic extract of the mycelial culture of Phellinus linteus significantly protected against hepatotoxins-
induced toxicity in primary cultured rat hepatocytes as seen from the decreased level of glutamic pyruvic transaminase released from
the injured hepatocytes. The methanolic extract of the mycelial culture of Phellinus linteus was subsequently fractionated with
n-hexane, ethyl acetate, n-butanol and water. Among these fractions, 100 μg/mL of the ethyl acetate fraction was the most active one.
The relative protections were 68.9 ± 5.3% in H2O2-injured hepatocytes and 46.8 ± 3.9% in galactosamine-injured hepatocytes,
respectively. The ethyl acetate fraction appeared to maintain the glutathione level which was decreased by the treatment of H2O2or
galactosamine and restored the level of RNA synthesis more than two times compared to galactosamine-injured hepatocytes. These
results suggest that the ethyl acetate fraction of the mycelial culture of Phellinus linteus protects hepatocytes from H2O2- or
galactosamine-induced injury by maintaining hepatic glutathione level and RNA synthesis as well.
34. Orally administered mycelial culture of Phellinus linteus exhibits antitumor effects in hepatoma cell-bearing mice.
Huang Hui-Yu; Chieh Shih-Yung; Tso Tim K; Chien Ting-Yi; LinHsin-Tang; Tsai Ying-Chieh
Journal of Ethnopharmacology 2011;133(2):460-6
http://www.ncbi.nlm.nih.gov/pubmed/20951789
Abstract
The aim of this studywas to evaluate the anticancer effect of a mycelial culture from Phellinus linteusPL-7 (MCPL-7) and to elucidate
its potential mechanism in vivo.
Materials and methods
SCIDCB-17 mice received a transplant of Hep3B cells followed by daily MCPL-7administrations for 8 weeks. Following tumor
implantation, groups C–E were subcutaneously administered 50 mg/kg, 100 mg/kg, or 250 mg/kgMCPL-7 powder per day, respectively,
for 8 weeks. Groups A and B receivedsaline solution subcutaneously for 8 weeks.
Results
MCPL-7 administration induced a significant reduction in tumor size and was associated with a significant increase in T cell
numbers; IL-12, IFN-γ and TNF-α secretion; NK cell activity; and phagocytic ability. Therefore, increased numbers of CD4+cells could
have been caused by greater numbers of dendritic cells and macrophages inthe spleen. Furthermore, the activation of dendritic cells
and macrophages resulted in increased IL-12 secretion, which could upregulate NK cell activation. The increased secretion of IL-12,
IFN-γ,and TNF-α enhanced the activity and phagocytic ability of NK cells. Thus, MCPL-7 may provide apotential therapeutic approach
for both immunomodulatory and antitumor effects.
35. Phellifuropyranone A: A new furopyranonecompound isolated from fruit bodies of wild Phellinus linteus
Kazuo Kojima, Takamasa Ohno, Makoto Inoue, Hajime Mizukami, and Akito Nagatsu
Chem. Pharm. Bull. 56(2) 173—175 (2008)
http://www.jstage.jst.go.jp/article/cpb/56/2/173/_pdf
Abstract
A new furopyranone,phellifuropyranone A, was isolated from fruit bodies of wild Phellinus linteus as well as phelligridin G, and their
chemical structures were determined by various spectroscopic methods including measurement of NMR spectra.Phellifuropyranone A
together with meshimakobnol A and meshimakobnol B showed antiproliferative activity against mouse melanoma cells and human
lung cancer cells in vitro.
36. Phelligridins C-F: Cytotoxic pyrano[4,3-c] [2]benzopyran-1,6-dione and furo[3,2-c] pyran-4-onederivatives from the fungus
Phellinus igniarius
Mo S ;Wang S ; Zhou G ; Yang Y ; Li Y ; Chen X ; Shi J
Journalof natural products,67(5) : 823-8 2004
http://www.ncbi.nlm.nih.gov/pubmed/15165144
Abstract
Three unique pyrano[4,3-c][2]benzopyran-1,6-dione derivativesand a new furo[3,2-c]pyran-4-one, named phelligridins C-F (2-5),
together with hispolon (8), (E)-4-(3,4-dihydroxyphenyl)but-3-en-2-one (9),4-hydroxybenzaldehyde, protocatechualdehyde, syringic acid,
protocatechuic acid, caffeic acid, isoergosterone, and octadecyl ferulate were isolated and identified from the ethanolic extract of
Phellinus igniarius. Their structures were determined by spectroscopic methods including IR, MS, and 1D and 2D NMR experiments.
The structures of the new compounds were characterized as3-(4-hydroxystyryl)-8,9-dihydroxypyrano[4,3-c]isochromene-4-one (2),3-(3,4-
hydroxystyryl)-8,9-dihydroxypyrano[4,3-c]isochromene-4-one (3),8,9-dihydroxy-3-{5',6'-dihydroxy-5-methyl-3-oxo-spiro[fural-2(3H),1'-
indene]-2'-yl}-1H,6H-pyrano[4,3-c][2]benzopyran-1,6-dione(4), and(3Z)-3-(3,4-dihydroxybenzylidene)-6-(3,4-dihydroxystyryl)-2,3-dihydro-2-
methoxy-2-(2-oxo-propyl)furo[3,2-c]pyran-4-one(5), respectively. Some compounds including 2 and 3 showed in vitro selective
cytotoxicity against a human lung cancer cell line (A549) and a liver cancer cell line (Bel7402). Possible biogenetic sequences to the
formation of 1-9 are postulated.
37. Phellinus linteus extract sentisizes advanced prostate cancer cells to apoptosis in Athymic nude mice
Takanori Tsuji, Wei Du, Takashi Nishioka, Lihua Chen, Daisuke Yamamoto, Chang Yan Chen
Department of Radiation oncology, Beth Israel Deaconess Medical Center, HARVARD MEDICAL SCHOOL, Boston, Massachusetts, USA
PloS ONEMarch 2010, Volume 5, Issue 3 e9885, 1-6
http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0009885
Abstract
Phellinus linteus (PL) mushroom possesses anti-tumor property. Wepreviously reported that the treatment with PL caused cultured
human prostatecancer cells to undergo apoptosis. To further studying the mechanisms ofPL-mediated apoptosis, we performed
xenograft assay, together with in vitro assays, to evaluate the effect of PL on the genesis and progression of thetumors form the
inoculation of prostate cancer PC3 or DU145 cells. After theinoculation, nude mice were injected with PL every two days for 12 days.
Although PL treatment did not prevent the formation of the inoculated tumors, the growth rate of the tumors after PL treatment was
dramatically attenuated.We then tested the effect of PL on the tumors 12 days after the inoculation.After inoculated tumors reached a
certain size, PL was administered to the miceby subcutaneous injection. The histochemistry or immunochemistry analysisshowed
that apoptosis occurred with the activation of caspase 3 in the tumorsformed by inoculating prostate cancer DU145 or PC3 cells. The
data was in agood agreement with that from cultured cells. Thus, our in vivo study suggeststhat PL not only is able to attenuate tumor
growth, but also to cause tumorregression by inducing apoptosis.
38. Phellinus linteus sensitizes apoptosis induced by doxorubicin in prostate cancer
L Collins, T Zhu, J Guo, Z J Xiao, and C-Y Chen
British Journal of Cancer 2006 August 7; 95(3): 282–288
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360641/
Abstract
It has been demonstrated that the Phellinus linteus (PL) mushroom, which mainly consists of polysaccharide s, possesses antitumour
activity. The mechanisms of PL against malignant growth remain unknown. The anticancer drugdoxorubicin (Dox) has been shown
to induce apoptosis via initiating a caspase cascade. In this investigation, we tested the effect of PL on Dox-induce dapoptosis in
prostate cancer LNCaP cells. We showed that PL or Dox, atrelatively low doses, does not induce apoptosis in the cells. However,
combination treatment with low doses of PL and Dox results in a synergisticeffect on the induction of apoptosis. In this apoptotic
process, caspases 8, 3and BID are cleaved, and the addition of caspase inhibitor z-VADfmk completelyblocks apoptosis. In addition, JNK
is activated in response to PL or the combination treatment in LNCaP cells. The suppression of JNK partially inhibitsthe induction of
apoptosis elicited by the co-treatment. These findings indicate that PL has a synergistic effect with Dox to activate caspases inprostate
cancer LNCaP cells. Our study also suggests that PL has therapeutic potential to augment the magnitude of apoptosis induced by
antiprostate cancer drugs.
39. Phellinus linteus suppresses growth, angiogenesis and invasive behavior of breast cancer cellsthrough the inhibition of AKT
signaling
DSliva, A Jedinak, J Kawasaki, K Harvey and V Slivova
BritishJournal of Cancer (2008) 98, 1348–1356. doi:10.1038/sj.bjc.6604319 www.bjcancer.co
Publishedonline 25 March 2008
http://www.nature.com/bjc/journal/v98/n8/abs/6604319a.html
Abstract
The antitumor activity of a medicinal mushroom Phellinus linteus (PL), through the stimulationof immune system or the induction of
apoptosis, has been recently described.However, the molecular mechanisms responsible for the inhibition of invasive behavior of
cancer cells remain to be addressed. In the present study, we demonstrate that PL inhibits proliferation (anchorage-dependent growth)
as well as colony formation (anchorage-independent growth) of highly invasive human breast cancer cells. The growth inhibition of
MDA-MB-231 cells is mediated by the cell cycle arrest at S phase through the upregulation of p27Kip1 expression. Phellinus linteus also
suppressed invasive behavior of MDA-MB-231 cells by the inhibition of cell adhesion, cell migration and cell invasion through the
suppression of secretion of urokinase-plasminogen activator from breast cancer cells. In addition, PL markedly inhibited the early
event in angiogenesis, capillary morphogenesis of the human aorticendothelial cells, through the downregulation of secretion of
vascular endothelial growth factor from MDA-MB-231 cells. These effects are mediated bythe inhibition of serine-threonine kinase
AKT signaling, because PL suppressed phosphorylation of AKT at Thr308 and Ser473 in breast cancer cells. Taken together, our study
suggests potential therapeutic effect of PL against invasive breast cancer.
40. Pro- and antioxidative properties of medicinal mushroom extracts
Song Wei, Leo J L D Van Griensve
International Journal of Medicinal Mushrooms(2008)Volume: 10, Issue: 4, Pages: 315-324
http://www.begellhouse.com/journals/708ae68d64b17c52,74677e1376d0a2ef,3f82c0ed39aeca5b.html
Abstract
Hot water extracts of 2 groups of medicinal mushrooms have been tested from thegen- era Agaricus, Antrodia, Auricularia, Coprinus,
Cordyceps, Hericium,Grifola, Ganoderma, Lentinus, Phellinus, and Trametes for ROS-generating activity in human cells and for DPPH-
TEAC antioxidant activity. Group 1 comprised 39 commercial extracts (7 species), and group 2 comprised 12 fruiting body extracts made
from 11 different species of culinary-medicinal mushrooms.For both groups, the ROS-generating activity and the antioxidant activity
were strongly correlated, as were their respective polysaccharide and polyphenol contents. The extracts differ in their amounts of the
latter components but not in the ratio of the two. The slopes of the correlation curves were different forboth groups, which is related to
the higher polyphenol content of the commercial extracts. It is suggested that possible excess cell defense-related intracellular ROS
generated by mushroom extracts may be downregulated by the antioxidant components present in the same extracts.
41. 41. Protein-bound polysaccharide from Phellinus linteus induces G2/M phase arrest and apoptosis in SW480 human colon cancer
cells
Ge Li, Dong-Hee Kim, Tae-Dong Kim, Byoung-Jeon Park, Hae-Duck Park, Jong-Il Park, Min-Kyun Na, Hwan-Chul Kim,Nam-Doo Hong,
Kyu Lim, Byung-Doo Hwang, Wan-Hee Yoon
Cancer Letters 216 (2004): 175-181
http://www.cancerletters.info/article/S0304-3835(04)00562-2/abstract
Abstract
The cytotoxic mechanism of protein-bound polysaccharide isolated from Phellinus linteus(PL, Mesima) has been investigated. PL
inhibited the proliferation and colony formation of SW480 human colon cancer cells. Flow cytometry analysis showed that PL increased
the populations of both apoptotic sub-G1 and G2/M phase. The result obtained fromTUNEL assay corroborated apoptosis which was shown
in flow cytometry. Westernblot analysis suggested that PL-induced apoptosis and growth inhibition were associated with decrease in
Bcl-2, increase of the release of cytochrome c, and reduced expression of cyclin B 1. These results suggest that PL has adirect
antitumor effect through apoptosis and cell cycle blockade in certain cancer cells
42. Proteoglycan isolated from Phellinus linteus activate murine B lymphocytes via protein kinase C and protein tyrosine kinase
Gi-Young Kim, Soon-Kew Park, Min-Ki Lee, Sang-Hwa Lee Yang-Hyo Oh, Jong-Young Kwak Sik Yoon, Jae-Dong Lee and Yeong-Min
Park
International Immunopharmacology 2003 Sep; 3:1281-92
http://www.sciencedirect.com/science/article/pii/S1567576903001152
Abstract
Medicinal mushrooms are increasingly used to treat a wide variety of disease processes. Aqueous extract from the fruiting body or
mycelia of Phellinus linteus has been reported to produce antitumor and immunomodulatory activities in vivoand in vitro. However, the
therapeutic mechanism has not been known. In the present study, we investigated whether proteoglycan (PL) isolated from
P. linteus has an effect on the immunomodulatory activities of the murine splenic lymphocytes (MSLs). Treatment with PL caused a
four-fold augmentation in [3H]thymidine incorporation compared to untreated control groupin MSLs. Flow cytometric analysis indicated
that the affected cell population was mainly CD19+ cells, but not CD3+ cells. These datasuggested that the main target of PL was the B
cells, but not T cells. PL alsoenhanced the expression of co-stimulatory molecules, CD80 and CD86, in murine Bcells in a time-
dependent manner. Accordingly, we investigated if intracellular[Ca2+] and reactive oxygen intermediates (ROI) were the principal
downstream components that contributed to PL-induced activation, with respectto both increases of proliferation and induction of co-
stimulatory molecules. However, PL has no influence on the [Ca2+] concentration and the ROI formation in murine B cells, whereas
the genistein, protein tyrosine kinase(PTK) inhibitor or staurosporine, protein kinase C (PKC), blocked the proliferationand the
induction of co-stimulatory molecules, CD80 and CD86, in B cells stimulated with PL. Taken together, these data suggest that PL is a
biological response modifier that stimulates proliferation and expression ofco-stimulatory molecules in B cells, probably by regulating
PTK and PKC signaling pathways.
43. Proteoglycan isolated from Phellinus linteus induces toll-like receptors 2- and 4-mediatedmaturation of murine dendritic cells
via activation of ERK, p38, and NF-kappaB
Kim Gi-Young ; Han Myung-Geum ; Song Yung-Sun ; Shin Byung-Cheul ; Shin Yong-Ii ; Lee Hee-Jeong ; Moon Dong-Oh ; Lee Chang-
Min; Kwak Jong-Young ; Bae Yoe-Sik ; Lee Jae-Dong ; Park Yeong-Min
BiolPharm Bull,27(10):1656-62 2004
http://www.jstage.jst.go.jp/article/bpb/27/10/1656/_pdf
Abstract
Mushroom polysaccharides are increasingly being utilized to treat a wide variety of diseases. Phellinus linteus proteoglycan (PL) has
been reported to have anti-tumor and immunomodulatory properties. However,the cellular and molecular mechanism underlying its
therapeutic effect is poorly understood. In this study, we investigated whether PL induces the phenotypic and functional maturation of
murine bone marrow-derived dendritic cells (DC) and the possibility that Toll-like receptors (TLRs), which are known to be involved in
immune-related responses, may be the receptor(s) of PL. The expression of surface molecules, including major histocompatibility
complex(MHC) class II and CD86, increased on DC that were stimulated in adose-dependent manner with PL, in comparison with
unstimulated DC. Furthermore, PL increases the production of IL-12 by DC, as well as the IL-2 secretion and proliferation of allogeneic
T cells. In addition, the activities of PL on DC were significantly reduced by treating the cells with anti-TLR2 or anti-TLR4 antibody (Ab)
prior to PL, suggesting that both of them are possible receptors of PL. Also, maturation of DC by PL was able to directly activate mitogen
activated protein kinases (MAPKs), such as ERK½ and p38, and the nuclear transcription factor NF-κB p65. Also, the pretreatment of
DC within hibitors of NF-κB p65, and ERK and p38 MAPK signal pathways inhibited PL-induced up-regulation of surface molecules, such
as MHC class II and CD86,and IL-12 production. Our results demonstrated that PL stimulation could induce the phenotypic and
functional maturation of DC via TLR2 and/or TLR4 mediated-NF-κB, ERK and p38 MAPK signal pathways.
44. 44. Proteoglycan isolated from Phellinus linteus inhibit tumor growth through mechanisms leading to an activation of CD 11c+CD8+
DC and type I Helper T cell-dominant immune state
Kim GY, Oh WK, Shin YI, Park YC, Ahn SC, Lee JD, Bae YS, Kwak JY, Park YM
FEBS Lett 2004 Oct; 576:391-400
http://www.ncbi.nlm.nih.gov/pubmed/15498569
Abstract
Dendritic cells (DC) are known to not only induce the activation of T cells, but are alsoassociated with the polarization of T cells. This
study investigated whether ornot proteoglycan (PG) isolated from Phellinus linteus induces thephenotypic and functional maturation of
CD11c+ DC in vitro and in vivo. PG wasfound to induce the phenotypic and functional maturation of bone marrow-derivedDC via Toll-
like receptors (TLR) 2 and 4 in vitro. Administration of PG in vivo strongly inhibited the MCA-102 tumor growth and increase in vivo.
The ratio of CD8+ DC to CD8- DC increased, and PG enhanced IL-12 and IFN-gamma production,and expression of surface molecules
including major histocompatibility complexes (MHC) classes I, MHC II, CD80, and CD86 in MCA-102-challenged mice.PG also caused a
marked increase in the production of Th (helper T cells)-1cytokine (IFN-gamma) and a decrease in the production of Th-2 cytokine (IL-
4) by splenic cells and inguinal lymph node cells in MCA-102 tumor-bearing mice.Furthermore, PG stimulated the proliferation of
CD4+ and CD8+ T cells. In addition, a combination of PG and tumor lysate-pulsed DC inhibited completely the growth of MCA-102 cells
in tumor-bearing mice. These results indicate that the administration of PG inhibited the tumor growth through a mechanism
leading to a Th-1 dominant immune state and the activation of CD11c+ CD8+ DC.
45. Purification and characterization of acidic proteo-heteroglycan from the fruiting body of Phellinus linteus (Berk. & M.A. Curtis)
Teng
Kim GY , Park HS , Nam BH , Lee SJ , Lee JD
Bioresour Technol 2003 Aug ; 89: 81-7
http://www.sciencedirect.com/science/article/pii/S0960852402002730
Abstract
Phellinus linteus is a well-known oriental medicinal fungusthat has various biological activities such as stimulation of humoral and
cell mediated immunity, anti-mutagenicity activity, and anti-cancer activity. The process of isolating and purifying a water soluble
glycan from P. linteus was achieved by hot water extraction, filtration, solvent precipitation, dialysis,and freeze-drying. Acidic fractions
of the polysaccharide were separated from crude polysaccharides by DEAE-cellulose anion exchange chromatography at 0.4 MNaCl. The
molecular weight of the proteo-heteroglycan after Sepharose CL-4B gelfiltration chromatography was about 150,000. The acidic proteo-
heteroglycan consisted of 72.2% polysaccharide and 22.3% protein. The sugar of the proteo-heteroglycanwas composed of mannose,
galactose, glucose, arabinose, and xylose. The amino acid pattern showed that the fractions contained large amounts of asparticacid,
glutamic acid, alanine, glycine, and serine. The fractions for bothα-glycan at 860 cm-1 and β-glycan at 910 cm-1 had the characteristics
of IR spectrum absorption as compared to those for β-glucan derived from Lentinus edodes. A 13C and 1H NMRspectroscopy showed that
the acidic proteo-heteroglycan was a noble biomolecule mixed both α- and β-linkages, and a (1,6) branched type (1,3) glycan.
46. Spontaneous regression of a large hepatocellular carcinoma with skull metastasis
Nam SW, Han JY,Kim JI, Park SH, Han NI, Yang JM, Kim JK, Choii SW, Lee YS, Chung KW, Sun HS
J Gastroenterol 2005 Mar;20(3):488-92
http://www.ncbi.nlm.nih.gov/pubmed/15740500
Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. This case of a 65-year-old Korean man with HCC
and metastatic frontal bone mass that regressedafter radiotherapy for frontal bone mass without any other therapeutic modalities is
described. The clinical diagnosis of HCC was made because of the presence of a liver mass on abdominal computed tomography (CT)
scan, high serum alpha-fetoprotein value and tissue diagnosis on frontal bone biopsy. Thepatient refused any other recommended
treatments, but accepted the radiation therapy due to a painful frontal bone mass, and ingested mushroom called Phellinus linteus for
one and a half years. Ten months after radiation therapy,he experienced a reduction in size of the frontal bone mass and improvement
of lesions in the liver, sternum and ribs. The patient is alive and in goodcondition without any symptoms or tumor aggravation in
August 2002. It wasconcluded that a rare case of spontaneous regression of HCC had occurred.
47. Structural analysis of water-soluble Polysaccharide PIP1, extracted from the cultured mycelium of Phellinus igniarius
Ming-Jiang WU De-zhi JIANG, Tie-mei LIU and Li-ping ZHANG
Chemical Research in Chinese Universities 2006; 6(22),708-711
http://www.sciencedirect.com/science/article/pii/S1005904006601955
Abstract
Water-solublecrude polysaccharide (PIP) was extracted from cultured mycelium of the fungus Phellinus igniarius.After ethanol
precipitation and sepharose CL-6B gel filtration,the fraction of PIP1 was obtained, which was shown to be ahomogeneous
polysaccharide by means of high-performance liquid chromatography.The structure of PIP1was determined by using several methods.
GC analysis indicates that PIP1 is composed of the monosaccharides ofglucose, galactose, and mannose. Their molar ratio is 3. 70: 4.
06: 1. 00. Themolar weight was estimated to be 17 kd via HPLC. IR, GC, partialhydrolysis with acid, periodate oxidation, Smith
degradation, methylation, andGC-MS analysis were used for the structural analyses of PIP1 The results show that PIP1has a small
quantity of branch structure. Themain glycosidic linkage of PIP1 has a β-configuration. The mainchain is made up of a large mass of
glucose (1—>3) and few mannose(1—>4); the side chain is composed of glucose (1—>3) and galactose(1—>6); the nonre-duced end is
composed of galactose and glucose. The sidechains are branched at 6–0 of glucose (1—>3, 6) and mannose (1—>4, 6). Onan average,
there are three branches among 20 residues. It is presumable thatthe existence of 1, 3-linked Glc in the main and side chains is the
main reasonfor its higher antitumor activity.
48. Structural and biological study of carboxymehthylated Phellinus linteus polysaccharides
Il-YoonShin, Suyong Lee, In Young Bae, Sang-Ho Yoo, Hyeon Gyu Lee
J.Agric. Food Chem. 2007, 55, 3368-3372
http://pubs.acs.org/doi/abs/10.1021/jf063003p
Abstract
Polysaccharidesisolated from Phellinus linteus were chemically modified bycarboxymethylation, and the structural and physiological
properties of thederivative were investigated. ¹³C NMR spectroscopy showed that the polysaccharides extracted from P. linteus
contained (1-3)-β-glucans with a (1-6)-linkage. The carboxymethylation of the P.linteus polysaccharides was confirmed by Fourier
transform infrared spectroscopy, and the degree of substitutionwaso btained by the potent iometric titration, which was calculated to
be 0.63. The bronchoalveolar lavage experiments showed that the carboxymethylated derivative raised the nitric oxide production. In
addition, the carboxymethylation stimulated in vitro cytotoxic activity against the HT1080 cell line. Thus, the derivative exhibited
the enhanced activity of immune systems, which would beexplained by the improved water solubility and structural changes
by carboxymethylation. However, a slight decrease in the2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of the derivative was observed.
49. Suppression of Hepatocellular carcinoma growth in mice via Mycelia of Liquid- Cultured Phellinus linteus, isassociated with
inhibition of tumor cell growth and natural killer cellactivation
Hui-Yu Huang, Tim K. Tso, Hsiao-Li Chang, Shih-Yung Chien, Yu-Ting Hsieh and Shih-Yung Chien
The FASEB Journal 2007;21:852.4
http://www.fasebj.org/cgi/content/meeting_abstract/21/6/A1100-b
Abstract
Phellinus linteus is a perennial fungus which is selectively parasitic on Morus rubra. This fungus is known as the Chinese medicine,
Souou, and rich with polysaccharideand polysaccharide-protein complex. The aim of this study was to determine Phellinus linteus is
anti-tumor effect in a murinemodel of hepatocellular carcinoma ( HCC). Eight weeks old male SCID mice were transplanted with
Hep3B cells, followed by daily Phellinus linteus administration for 8 weeks. Phellinus linteus administration induced a significant
reduction in tumor size,improved survival rate, and was association with a significant increasein splenocytes. There was no
significant difference between groups was noted in any of the other serum cytokine level. However, Phellinus linteusadministration
induces a significant suppression of human HCC. This effect is mediated by induction of natural killer cell activation,along with
direct inhibition of tumor growth.
50. The apoptosis effect of hispolon from Phellinus linteus (Berkeley & Curtis) Teng on human epidermoid KB Cells
WeiChen, Fei-Yu He , Yong-Quan Li
Journal of ethnopharmacology 2006; 280-285
http://www.sciencedirect.com/science/article/pii/S0378874106000560
Abstract
Phellinus linteus (Berkeley & Curtis) Teng, a well-known fungus of the genus Phellinus in the family of Hymenochaetaceae, is being
increasingly used to treat a wide variety of disease processes such asoral ulcer, gastroenteric disorder, inflammation, lymphatic
disease, and various cancers. However, the mechanism underlying its anti-oral cancer effect is poorly understood. In the present
study, we prepared the ethanol extract of Phellinus linteus as a crude drug, and then obtained the active component hispolon by
bioassay-guided isolation. Hispolon showed a dose-dependent inhibition of human epidermoid KB cell proliferation with IC50 of
4.62 ± 0.16 μg/ml. Furthermore, it was revealed that hispolon could induce human epidermoid KBcell apoptosis with the characteristic
of a DNA ladder, and with a significantincrease of sub-G1. This process was accompanied by the collapse ofmitochondrial membrane
potential, the release of cytochrome c and the activation of Caspase-3. These results demonstrated that hispolon induced the death of
KB cells through a mitochondria mediated apoptotic pathway. We propose that Phellinus linteus and its effective components could be
used as ananti-oral cancer drug for future studies.
51. The inhibitory effectof polysaccharide isolated from Phellinus linteus on tumor growth and metastasis
SangBae Han, Chang Woo Lee, Young Jin Jeon, Nam Doo Hong, Ick Dong Yoo, Kyu-Hwan Yang, Hwan Mook Kim
Immunopharcology 1999 Feb,41:157-64
http://www.sciencedirect.com/science/article/pii/S0162310998000630
Abstract
It was previously reported that polysaccharides (PL) isolated from Phellinus linteus strongly stimulates cell-mediated and humoral
immunity. This studywas undertaken to investigate the immunochemotherapeutic activity of PL against tumor growth and metastasis.
PL alone significantly prolonged the survival rateof B16F10 –implanted mice, inhibited tumor growth in NCI-H23-implanted nude,and
reduced the frequency of pulmonary metastasis of B16F10 melanoma. Adriamycin significantly inhibited tumor growth, but only slightly
inhibited metastasis. The combination therapy with PL and adriamycin was more effectivein inhibiting tumor growth, but not
metastasis. PL did not induce direct toxicity in cancer cells,which is characteristic of immunochemotherapeutic. In conclusion, PL
might be of use in immunochemotherapy of cancer because of itseffective activities on tumor growth and metastasis through the
immunopotentiation of the patients without toxicity.
52. The roles of ERK1/2 and p38 MAP kinases in the preventive mechanisms of mushroom Phellinus linteus against the inhibition
of gap junctional intercellular communication by hydrogen peroxide
Jong-Ho Cho, Sung-Dae Cho, Hongbo Hu, Sung-Hoon Kim, Song Koo Lee, Yong-Soon Lee, Kyung-Sun Kang
Carcinogenesis 2002 Jul,23; 1163-9
Abstract
Modulation of gap junctional intercellular communication (GJIC) is a known cellular event associated with tumor promotion. The
present study was undertaken to test the potential preventive effect of mushroom Phellinus linteus extract (PL) on the inhibition of
GJIC, induced by hydrogen peroxide (H2O2), in WB-F344 rat liver epilial cells (WB cells). Cells were pre-incubated with PL (5 and
25µg/ml) for 24 h and this was followed by co-treatment with PL and H2O2 (500 µM) for 1 h. PL (at 5 and 25 µg/ml) prevented the
inhibition of GJIC and blocked the hyper-phosphorylation of connexin 43 by H2O2. Moreover, H2O2 activated p38 kinase,
extracellularsignal-regulated protein kinases (ERK)1/2 and c-Jun N-terminal kinase (JNK) in WB cells. The present study indicates
that PL is able to inactivate both ERK 1/2 and p38 MAP kinases. However, PL did not affect the JNK pathway. For thisreason, to
elucidate the relation between kinases and GJIC, we treated cells with PD98059 (an MEK inhibitor) and SB202190 (a p38 kinase
inhibitor). These inhibitors were also found to prevent the inhibition of GJIC induced by H2O2, which suggests that PL may act as a
natural anticancer product by preventing the inhibition of GJIC throughh the inactivation of ERK1/2 and p38 MAP kinases. In addition,
our results indicate that the p38 kinase signaling pathway may be closely related functionally to the gap junction in rat liver epithelial
cells.
53. 53. Tumor-inhibitory and liver-protective effects of Phellinus igniarius extracellular polysaccharides
Wei Dong, Li Ning, Wei-dong Lu, Cui-cui Li, Rui-peng Chen, Xiao-ning Jia, Lin Wang and Li-zhong Guo
World J Microbial Biotechnol (2009) 25:633-638
http://www.springerlink.com/content/g8p6553669364560/
Abstract
The tumor-inhibitory andliver-protective effects of crude extracellular polysaccharides (EPS) extracted from the liquid mycelial culture
of the mushroom Phellinus igniarius were studied in mice. The mice were injected with murine sarcoma S180 and murine hepatoma
H22. Crude EPS at 100, 200, 400 mg kg−1 body weight was administered to EPS groups each day in the twelve consecutive days. The
result showed that EPS 200 mg kg−1 body weight significantly inhibited S180 and H22 at 65.0 and 46.3%, respectively. Moreover,EPS
could not only keep the numbers of WBC, RBC, PLT and the concentration ofHGB in a normal range, but also normalize the activities of
AST, ALT and ALP.For example, in EPS-treated mice, AST significantly reduced with the percentage of A/G reverse in S180 (P < 0.05)
and H22 (P < 0.01) when the mice took EPS 200 mg kg−1 body weight. In conclusion, it was remarkable that P. igniariusE PS exhibited
antitumor activity related to dosage and protected liver function by sustaining the blood routine as well as keeping the blood
biochemical indexes normal.
54. Antiproliferative and antimetastatic effects of the ethanolic extract of Phellinus igniarius (Linnearus:Fries) Quelet
Tuzz-Ying Song, Hung-Chi Lin, Nae-Cherng Yang, Miao-Lin Hu
Journal of Ethnopharmacology 115 (2008) 50-56
http://www.sciencedirect.com/science/article/pii/S0378874107004679
Abstract
Aim of this study
Phellinus igniarius (Linnearus: Fries) Quelet (Phellinus igniarius) has been used in oriental countries for treatment of various diseases
including cancer. However, it is unclear how Phellinus igniarius exerts anticancer effects.
Materials and methods
In this study the ethanolic extract from the fruiting body of Phellinus igniarius (EEPI) was used to evaluate the antiproliferative and
antimetastatic effects in human hepatocarcinoma SK-Hep-1cells and rat heart vascular endothelial cells (RHE cells).
Results
We found that EEPI inhibited the proliferation of both cell lines in a dose-dependent manner, and the IC50 values at 48 h were 72 and
103 μg/ml for SK-Hep-1 cells and RHE cells, respectively. EEPI at non- or sub-cytotoxic concentrations (25–100 μg/ml) markedly
inhibited the migration and invasion of SK-Hep-1 cells. EEPI added at 25 μg/ml significantly decreased the secretion of matrix
metalloproteinase-2 (MMP-2)(49%, p < 0.01) and vascular endothelial growth factor (VEGF) (13%, p < 0.05) in SK-Hep-1 cells. EEPI at 25 μ
g/ml completely inhibited matrigel-induced tube formation in RHE cells. Importantly, EEPI (25 or 50 μg/ml) in combination with
oxaliplatin (Oxa) or 5-flurouracil (5-FU) synergistically inhibited the proliferation of SK-Hep-1 cells.
Conclusion
These results demonstrate the antiproliferative and antimetastatic effects of EEPI invitro and the potential of EEPI as an adjuvant for
chemotherapy.