Scientific Researches On:
Ganoderma Lucidum (Reishi Mushroom)
USA National Center for Biotechnology Information
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61:
Acta Pharmacol Sin. 2004 Jun;25(6):833-8.
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Antitumor and anti-angiogenic activity of Ganoderma
lucidum polysaccharides peptide.
Cao QZ,
Lin ZB.
Department of Pharmacology, Health Science Center,
Peking University, Beijing 100083, China.
AIM: To investigate the antitumor and anti-angiogenic
activity of Ganoderma lucidum polysaccharides peptide (GLPP).
METHODS: Antitumor effect of GLPP was observed in
tumor-bearing mice in vivo. At the same time, the
effects of GLPP on proliferation of tumor cells and
human umbilical cord vascular endothelial cell (HUVEC)
were detected by MTT assay in vitro. Subsequently,
spleen lymphocytes proliferation of nude mice was
stimulated by LPS or ConA. To investigate the anti-angiogenic
effect of GLPP, GLPP 80 microg per disc and GLPP-treated
serum 10 microL per disc were added to the chick
chorioallantoic membrane (CAM) respectively in vivo.
RESULTS: GLPP 50, 100, and 200 mg/kg inhibited growth of
Sarcoma 180 in BALB/c mice markedly by 35.2 %, 45.2 %,
and 61.9 %, respectively. GLPP which was directly added
to the cultured medium did not inhibit PG cell
proliferation in vitro; but GLPP-treated serum 50, 100,
200 mg/kg potently inhibited PG cell proliferation by
22.5 %, 26.8 %, and 30.3 %, respectively; and reduced
the xenograft (human lung carcinoma cell PG) in BALB/c
nude mice greatly in vivo by 55.5 %, 46.0 %, and 46.8 %,
respectively. Lymphocytes proliferation of nude mice
could be stimulated by LPS 5 mg/L but not by ConA 2.5
mg/L, indicating that GLPP could not promote the T
lymphocyte proliferation and neutral red phagocytosis of
peritoneal macrophages of nude mice. The CAM assay
showed that GLPP and GLPP-treated serum had anti-angiogenic
effect. GLPP (1, 10, and 100 mg/L) inhibited HUVEC
proliferation in vitro with the inhibitory rate of 9.4
%, 15.6 %, and 40.4 %, respectively. CONCLUSION: GLPP
has antitumor and anti-angiogenic activity. The
anti-angiogenesis of GLPP may be a new mechanism
underlying its anti-tumor effects.
PMID: 15169641 [PubMed - indexed for MEDLINE]
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Cytotoxic activity of methanol extracts from
Basidiomycete mushrooms on murine cancer cell lines.
Tomasi S,
Lohézic-Le Dévéhat F,
Sauleau P,
Bézivin C,
Boustie J.
Laboratoire de Pharmacognosie et de Mycologie, UPRES
2234 "Synthèse et extraction de molécules a visée
thérapeutique", Faculté de Pharmacie, Rennes, France.
sophie.tomasi@univ-rennes1.fr
Crude methanol extracts of 58 mushroom species were
screened for their cytotoxic activities against two
murine cancer cell lines, L1210 and 3LL, using the
tetrazolium assay. A majority of extracts (74%)
exhibited IC50 > 100 microg/ml against both cell lines.
A most marked activity against one of the cell lines was
noted for nine species (14% of the tested species).
While Amanitales and Russulales tested were not found
active, Polyporales and Boletales gave better results.
Four species exhibited a significant cytotoxic activity
(IC50 < or = 20 microg/ml) against at least one of the
two murine cancer cell lines (Ganoderma lucidum,
Meripilus giganteus, Suillus granulatus, S. luteus). The
last one had never been investigated for its cytotoxic
compounds before.
Publication Types:
PMID: 15125575 [PubMed - indexed for MEDLINE]
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Ganoderma lucidum inhibits proliferation and induces
apoptosis in human prostate cancer cells PC-3.
Jiang J,
Slivova V,
Valachovicova T,
Harvey K,
Sliva D.
Cancer Research Laboratory, Methodist Research
Institute, E504, Indianapolis, IN 46202, USA.
Ganoderma lucidum (Reishi), an oriental medical
mushroom, has been widely used in Asian countries for
centuries to prevent or treat different diseases,
including cancer. However, the mechanism(s) responsible
for the effects of Ganoderma lucidum on cancer cells
remain to be elucidated. We have previously demonstrated
that Ganoderma lucidum down-regulated the expression of
NF-kappaB-regulated urokinase plasminogen activator (uPA)
and uPA receptor (uPAR), which resulted in suppression
of cell migration of highly invasive human breast and
prostate cancer cells. In this study, we investigated
the effects of Ganoderma lucidum on cell proliferation,
cell cycle, and apoptosis in human prostate cancer cells
PC-3. Our data demonstrate that Ganoderma lucidum
inhibits cell proliferation in a dose- and
time-dependent manner by the down-regulation of
expression of cyclin B and Cdc2 and by the up-regulation
of p21 expression. The inhibition of cell growth was
also demonstrated by cell cycle arrest at G2/M phase.
Furthermore, Ganoderma lucidum induced apoptosis of PC-3
cells with a slight decrease in the expression of NF-kappaB-regulated
Bcl-2 and Bcl-xl. However, the expression of
proapoptotic Bax protein was markedly up-regulated,
resulting in the enhancement of the ratio of Bax/Bcl-2
and Bax/Bcl-xl. Thus, Ganoderma lucidum exerts its
effect on cancer cells by multiple mechanisms and may
have potential therapeutic use for the prevention and
treatment of cancer.
Publication Types:
PMID: 15067330 [PubMed - indexed for MEDLINE]
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Effects of a genistein-rich extract on PSA levels in
men with a history of prostate cancer.
deVere White RW,
Hackman RM,
Soares SE,
Beckett LA,
Li Y,
Sun B.
Department of Urology, University of California, Davis,
School of Medicine, Sacramento, California 95817, USA.
OBJECTIVES: To determine whether supplemental amounts of
soy isoflavone (genistein-rich extract) would lower
prostate-specific antigen (PSA) levels more than 50% in
patients with prostate cancer (CaP). METHODS: A total of
62 men (mean age 73.6 years, range 61.4 to 89.3) with
histologically proven CaP who had two consecutive
elevated PSA readings were accrued during a 13-month
period. An open-label pilot study was conducted for 6
months in which the patients took capsules containing
the genistein-rich extract three times daily by mouth.
The subjects were in one of five groups: after radical
retropubic prostatectomy (n = 9), after radiotherapy (n
= 17), after both radical retropubic prostatectomy and
radiotherapy (n = 6), off-cycle during hormonal therapy
(intermittent hormones; n = 14), or active surveillance
(n = 16). The primary endpoint for the trial was a 50%
reduction in the PSA level at 6 months compared with
before treatment. RESULTS: Of the 62 men enrolled, 52
were available for evaluation at 6 months. Three
patients discontinued because of adverse events
(diarrhea) and seven because of personal choice. One of
52 patients had a more than 50% reduction in the PSA
level (1.9% response, 95% confidence interval 0.1% to
10.3%). An additional 7 patients had PSA reductions that
were less than 50%. All 8 patients with lower PSA levels
at 6 months were in the active surveillance (watchful
waiting) treatment subgroup. Repeated measure regression
models allowing for correlation between initial levels
and change also indicated a decline in PSA in this group
compared with other groups: 0 of 52 had a complete
response, 9 (17%) had a partial response, 8 (15%) had
stable disease, and 35 (67%) had disease progression. In
the 9 patients with a partial response, 6 had pathologic
findings that were moderately differentiated, 2 had
well-differentiated findings, and 1 had poorly
differentiated findings. Therefore, the response in this
group of patients did not appear to be driven by the
Gleason score. The total testosterone level was lowered
in one of the patients responding, but it was higher in
five others. CONCLUSIONS: A genistein-rich extract as
the sole treatment for CaP did not reduce PSA levels by
50% or more in 51 of 52 subjects. Thus, it does not
appear to be an effective treatment for CaP when given
alone. However, 8 of 13 evaluated patients in the active
surveillance group had either no rise or a decline in
PSA levels of less than 50%. More study is warranted for
those choosing active surveillance.
Publication Types:
PMID: 14972467 [PubMed - indexed for MEDLINE]
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Comment in:
Ganoderma lucidum ("Lingzhi"), a Chinese medicinal
mushroom: biomarker responses in a controlled human
supplementation study.
Wachtel-Galor S,
Tomlinson B,
Benzie IF.
Ageing & Health Group, School of Nursing, The Hong Kong
Polytechnic University, Kowloon, Hong Kong SAR, China.
Lingzhi (Ganoderma lucidum) is a woody mushroom highly
regarded in traditional medicine and is widely consumed
in the belief that it promotes health and longevity,
lowers the risk of cancer and heart disease and boosts
the immune system. However, objective scientific
validation of the putative health benefits of Lingzhi in
human subjects is lacking, and issues of possible
toxicity must be addressed. The present double-blinded,
placebo-controlled, cross-over intervention study
investigated the effects of 4 weeks Lingzhi
supplementation on a range of biomarkers for antioxidant
status, CHD risk, DNA damage, immune status, and
inflammation, as well as markers of liver and renal
toxicity. It was performed as a follow-up to a study
that showed that antioxidant power in plasma increased
after Lingzhi ingestion, and that 10 d supplementation
was associated with a trend towards an improved CHD
biomarker profile. In the present study, fasting blood
and urine from healthy, consenting adults (n 18; aged
22-52 years) was collected before and after 4 weeks
supplementation with a commercially available
encapsulated Lingzhi preparation (1.44 g Lingzhi/d;
equivalent to 13.2 g fresh mushroom/d) or placebo. No
significant change in any of the variables was found,
although a slight trend toward lower lipids was again
seen, and antioxidant capacity in urine increased. The
results showed no evidence of liver, renal or DNA
toxicity with Lingzhi intake, and this is reassuring.
The present study of the effects in healthy,
well-nourished subjects provides useful, new scientific
data that will support controlled intervention trials
using at-risk subjects in order to assess the
therapeutic effect of Lingzhi in the promotion of
healthy ageing.
Publication Types:
PMID: 14756912 [PubMed - indexed for MEDLINE]
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Ganoderma lucidum (Reishi) in cancer treatment.
Sliva D.
Cancer Research Laboratory, Methodist Research
Institute, Indianapolis, IN 46202, USA. d-silva@clarian.org
The popular edible mushroom Ganoderma lucidum (Reishi)
has been widely used for the general promotion of health
and longevity in Asian countries. The dried powder of
Ganoderma lucidum was popular as a cancer chemotherapy
agent in ancient China. The authors recently
demonstrated that Ganoderma lucidum inhibits
constitutively active transcription factors nuclear
factor kappa B (NF-kappaB) and AP-1, which resulted in
the inhibition of expression of urokinase-type
plasminogen activator (uPA) and its receptor uPAR.
Ganoderma lucidum also suppressed cell adhesion and cell
migration of highly invasive breast and prostate cancer
cells, suggesting its potency to reduce tumor
invasiveness. Thus, Ganoderma lucidum clearly
demonstrates anticancer activity in experiments with
cancer cells and has possible therapeutic potential as a
dietary supplement for an alternative therapy for breast
and prostate cancer. However, because of the
availability of Ganoderma lucidum from different
sources, it is advisable to test its biologic activity.
Publication Types:
PMID: 14713328 [PubMed - indexed for MEDLINE]
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Lucidenic acids P and Q, methyl lucidenate P, and
other triterpenoids from the fungus Ganoderma lucidum
and their inhibitory effects on Epstein-Barr virus
activation.
Iwatsuki K,
Akihisa T,
Tokuda H,
Ukiya M,
Oshikubo M,
Kimura Y,
Asano T,
Nomura A,
Nishino H.
K-Laboratories for Intelligent Medical Remote Services,
2266-22 Anagahora, Shimoshidami, Moriyama-ku, Nagoya
463-0003, Japan.
A new triterpene acid, lucidenic acid P (1a), and two
new triterpene acid methyl esters, methyl lucidenates P
(1b) and Q (2b), were isolated and characterized from
the fruiting body of the fungus Ganoderma lucidum. Their
structures were elucidated on the basis of spectroscopic
methods. In addition, eight known triterpene acids,
lucidenic acids A (3a), C (4a), D(2) (5a), E(2) (6a),
and F (7a) and ganoderic acids E (9a), F (10a), and T-Q
(11a), and six known triterpene acid methyl esters,
methyl lucidenates A (3b), D(2) (5b), E(2) (6b), F (7b),
and L (8b) and methyl ganoderate F (10b), were isolated
and identified from the fungus. All of the triterpenoids,
with the exception of 7a, were evaluated with respect to
their inhibitory effects on the induction of
Epstein-Barr virus early antigen (EBV-EA) by
12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji
cells, which is known to be a primary screening test for
antitumor promoters. All of the compounds tested showed
potent inhibitory effects on EBV-EA induction (96-100%
inhibition at 1 x 10(3) mol ratio/TPA).
Publication Types:
PMID: 14695801 [PubMed - indexed for MEDLINE]
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Biologic activity of spores and dried powder from
Ganoderma lucidum for the inhibition of highly invasive
human breast and prostate cancer cells.
Sliva D,
Sedlak M,
Slivova V,
Valachovicova T,
Lloyd FP Jr,
Ho NW.
Cancer Research Laboratory, Methodist Research
Institute, Clarian Health Partners Inc., Indianapolis,
IN 46202, USA. dsliva@clarian.org
OBJECTIVE: Ganoderma lucidum has been used in East Asia
as a home remedy to prevent or cure cancer. Furthermore,
Ganoderma lucidum is one of the herbs in the herbal
mixture PC-SPES that has become an alternative herbal
therapy for prostate cancer. Because the dried powder of
ganoderma is commercially available as a dietary
supplement itself, the purpose of this study was to
evaluate the biologic activity of samples of Ganoderma
lucidum from different sources. METHODS: Samples of
Ganoderma lucidum were characterized morphologically and
evaluated for their ability to inhibit cell migration of
highly invasive breast cancer MDA-MB-231 cells and
prostate cancer PC-3 cells. Because the inhibition of
cell motility is directly linked to the inhibition of
the signaling pathway for constitutively active NF-kappaB
in breast and prostate cancer cells, we determined how
different samples of Ganoderma lucidum inhibit
constitutively active NF-kappaB in a reporter gene
assay. RESULTS: Some of the samples of Ganoderma lucidum
demonstrated strong inhibition of cancer cell migration
comparable to the inhibition of constitutively active
NF-kappaB, whereas other samples showed less or no
activity in highly invasive estrogen receptor-negative
breast cancer cells or androgen receptor-negative
prostate cancer cells, respectively. Interestingly, we
did not find any correlation between the purity and
composition (spores versus powder) of Ganoderma lucidum
and biologic activity. CONCLUSIONS: Ganoderma lucidum
has demonstrated strong activity against breast and
prostate cancer cells. Nevertheless, the composition of
samples did not correlate with their ability to inhibit
cell migration and activation of NF-kappaB in vitro.
Publication Types:
PMID: 14499024 [PubMed - indexed for MEDLINE]
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Effects of ganopoly (a Ganoderma lucidum
polysaccharide extract) on the immune functions in
advanced-stage cancer patients.
Gao Y,
Zhou S,
Jiang W,
Huang M,
Dai X.
Institute of Food, Nutrition and Human Health, Massey
University, New Zealand.
Preclinical studies have established that the Ganoderma
lucidum polysaccharide (GLPS) fractions have potent
anti-tumor activity, which has been associated with the
immuno-stimulating effects of GLPS. However, it is
unclear whether GLPS has immuno-modulating effects in
humans in vivo. This study aimed to investigate the
effects of Ganopoly, the polysaccharides fractions
extracted from G. lucidum, on the immune function of
advanced-stage cancer patients. Thirty-four
advance-stage cancer patients were entered onto this
study, and treated with 1800 mg Ganopoly, three times
daily orally before meals for 12 weeks. Immune
parameters (cytokines, T cell subsets, mitotic response
to phytohemagglutinin (PHA) and natural killer activity)
were compared between baseline and after 12-week
treatment. Thirty patients are assessable for their
immune functions. Treatment of Ganopoly for 12 weeks
resulted in a significant (P < 0.05) increase in the
mean plasma concentrations of interleukin (IL-2), IL-6,
and interferon (IFN)-gamma, whereas the levels of IL-1
and tumor necrosis factor (TNF-alpha) were significantly
(P < 0.05) decreased. A marked variability among
patients with advanced-stage cancer was observed in the
numbers of each lymphocyte subset at baseline. The mean
absolute number of CD56+ cells was significantly (P <
0.05) increased after 12-week treatment of Ganopoly,
whereas the numbers of CD3+, CD4+, and CD8+ were just
marginally increased compared to baseline levels, with
the CD4:CD8 T cell ratios unchanged. PHA responses after
12-week treatment with Ganopoly were enhanced in most
patients, when compared to pretreatment baselines (P <
0.05). In addition, Ganopoly treatment resulted in a
significant increase (P < 0.05) in the mean NK activity
compared to baselines (34.5 +/- 11.8% vs 26.6 +/- 8.3%).
The present study indicates that Ganopoly enhanced the
immune responses in patients with advanced-stage cancer.
Clinical evaluations of response and toxicity are
ongoing.
Publication Types:
PMID: 12916709 [PubMed - indexed for MEDLINE]
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Submerged cultivation of Ganoderma lucidum biomass
and immunostimulatory effects of fungal polysaccharides.
Berovic M,
Habijanic J,
Zore I,
Wraber B,
Hodzar D,
Boh B,
Pohleven F.
National Institute of Chemistry, Hajdrihova 19,
Ljubljana 1001, Slovenia. marin.berovic@ki.si.
Original Ganoderma lucidum strain MZKI G97 isolated from
Slovenian forests was cultivated in a liquid substrate
based on potato dextrose and olive oil. The influences
of inoculum and oxygen partial pressure in batch and fed
batch cultivation in a 10-l laboratory stirred tank
reactor were studied. Fungal biomass was found to be
oxygen and shear sensible. Using a 17% (wet weight) 6
days old vegetative inoculum, 9.6 g l(-1) of dry biomass
in batch cultivation and 15.2 g l(-1) in fed batch
process were obtained. Extracellular (9.6 g l(-1)) and
intracellular (6.3 g l(-1)) polysaccharide fractions
were isolated. Extracellular polysaccharide fraction and
four intracellular polysaccharide fractions were
obtained. Polysaccharides were further separated by
ion-exchange, gel and affinity chromatography. The
isolated polysaccharides were mainly beta-D-glucanes.
Immunostimulatory effects of isolates were tested on
induction of cytokine (tumour necrosis factor alpha (TNF-alpha)
and interferon gamma (IFN-gamma)) synthesis in primary
cultures of human peripheral blood mononuclear cells (PBMC)
isolated from a buffy coat. The TNF-alpha inducing
activity is comparable with romurtide, which has been
used as a supporting therapy in cancer patients treated
with radiotherapy and/or chemotherapy.
Publication Types:
PMID: 12770506 [PubMed - indexed for MEDLINE]
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Synthesis of beta-(1-->6)-branched beta-(1-->3)
glucohexaose and its analogues containing an
alpha-(1-->3) linked bond with antitumor activity.
Ning J,
Zhang W,
Yi Y,
Yang G,
Wu Z,
Yi J,
Kong F.
Research Center for Eco-Environmental Sciences, Chinese
Academy of Sciences, PO Box 2871, Beijing 100085, PR
China. fzkong@mail.rcees.ac.cn
A beta-(1-->6)-branched beta-(1-->3)-glucohexaose,
present in many biologically active polysaccharides from
traditionally herbal medicines such as Ganoderma lucidum,
Schizophyllum commune and Lentinus edodes, was
synthesized as its lauryl glycoside 32, and its
analogues 18, 20 and 33 containing an alpha-(1-->3)
linked bond were synthesized. It is interesting to find
that coupling of a 3,6-branched acylated trisaccharide
trichloroacetimidate donor 9 with 3,6-branched acceptors
13 and 16 with 3'-OH gave the alpha-(1--> 3)-linked
hexasaccharides 17 and 19, respectively, in spite of the
presence of C-2 ester capable of neighboring group
participation. However, coupling of 9 with
4-methoxyphenyl 4,6-O-benzylidene-beta-D-glucopyranoside
(27) selectively gave beta-(1-->3)-linked
tetrasaccharide 28. Simple chemical transformation of
the tetrasaccharide 28 gave acylated tetrasaccharide
trichloroacetimidate 29. Coupling of 29 with lauryl
(1-->6)-linked disaccharide 26 with 3-OH gave
beta-(1-->3)-linked hexasaccharide 30 as the major
product. Bioassay showed that in combination with the
chemotherapeutic agent cyclophospamide (CPA), the
hexaose 18 at a dose of 0.5-1mg/kg substantially
increased the inhibition of S(180) for CPA, but
decreased the toxicity caused by CPA. Some of these
oligosaccharides also inhibited U(14) noumenal tumor in
mice effectively.
Publication Types:
PMID: 12713829 [PubMed - indexed for MEDLINE]
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Triterpene-enriched extracts from Ganoderma lucidum
inhibit growth of hepatoma cells via suppressing protein
kinase C, activating mitogen-activated protein kinases
and G2-phase cell cycle arrest.
Lin SB,
Li CH,
Lee SS,
Kan LS.
Graduate Institute of Medical Technology, College of
Medicine, National Taiwan University, 10016, Taipei,
Taiwan, ROC. sblin@ha.mc.ntu.edu.tw
The medicinal mushroom Ganoderma lucidum (G. lucidum)
has been used in the Orient for the prevention and
treatment of various diseases including cancer. Except
for the immune enhancing properties of its
polysaccharide constituent, very little is known about
the anticancer activity of another major constituent,
triterpenes. In this report, we studied the anticancer
mechanism of triterpene-enriched extracts from G.
lucidum. The triterpene-enriched fraction, WEES-G6, was
prepared from mycelia of G. lucidum by sequential hot
water extraction, removal of ethanol-insoluble
polysaccharides and then gel-filtration chromatography.
We found that WEES-G6 inhibited growth of human hepatoma
Huh-7 cells, but not Chang liver cells, a normal human
liver cell line. Treatment with WEES-G6 caused a rapid
decrease in the activity of cell growth regulative
protein, PKC, and the activation of JNK and p38 MAP
kinases. The changes in these molecules resulted in a
prolonged G2 cell cycle phase and strong growth
inhibition. None of these effects were seen in the
normal liver cells. Our findings suggest that the
triterpenes contained in G. lucidum are potential
anticancer agents.
Publication Types:
PMID: 12639703 [PubMed - indexed for MEDLINE]
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Antiperoxidative, anti-inflammatory, and
antimutagenic activities of ethanol extract of the
mycelium of Ganoderma lucidum occurring in South India.
Lakshmi B,
Ajith TA,
Sheena N,
Gunapalan N,
Janardhanan KK.
Amala Cancer Research Centre, Thrissur, Kerala, India.
Free radical mediated genetic instability is widely
thought to be a major etiological factor for initiation
of carcinogenesis. Mushrooms represent a largely
untapped source of powerful new pharmaceutical products.
In the present study, we examined the antiperoxidative,
anti-inflammatory, and antimutagenic activities of the
ethanol extract of the mycelium of a medicinal mushroom,
Ganoderma lucidum, occurring in south India.
Antiperoxidative activity was evaluated using
Fe(2+)-ascorbate-induced lipid peroxidation in rat liver
homogenate and a phorbol ester (croton oil)-induced
lipid peroxidation in mouse skin. Antiinflammatory
activity was evaluated against carrageenan-induced acute
and formalin-induced chronic inflammatory paw edema in
mouse and phorbol ester-induced mouse skin inflammation.
Antimutagenic activity was determined by the Ames
mutagenicity assay using histidine mutant of Salmonella
typhimurium strains TA 98, TA100, and TA102. Sodium
azide (NaN(3)), N-methyl-N-nitro-N-nitrosoguanidine (MNNG),
4-nitro-o-phenylenediamine (NPD), and benzo[a]pyrene (B[a]P)
were used as the mutagens. The extract showed
significant inhibition of Fe(2+)-induced peroxidation of
lipid in rat liver (IC(50) 510 +/- 22 microg/ml) and 37%
inhibition of croton oil-induced peroxidation on the
mouse skin at 20 mg/0.1 ml/skin. Carrageenan-induced
acute and formalin-induced chronic inflammatory edema
were inhibited by 56 and 60%, respectively, by the
extract at 1,000 mg/kg body wt (i.p). The extract at a
concentration of 5 mg/plate showed inhibition of
mutagenicity elicited by direct acting mutagens, NaN(3)
(55.5 and 75.7%) and MNNG (50.0 and 57.5%) for S.
typhymurium strains TA100 and TA102, respectively. The
extract at the same concentration also inhibited
mutagenicity elicited by NPD (52.4 and 64.2%) and B[a]P
(60.7 and 59.6%) for TA98 and TA100 strains,
respectively. The B[a]P was activated in the presence of
rat liver microsomal (S9) fraction. The results of our
study revealed that ethanol extract of Ganoderma lucidum
mycelium possessed significant antiperoxidative,
antiinflammatory, and antimutagenic activities. The
findings suggest a medicinal use for the ethanol extract
of the mycelium of G. lucidum occurring in South India.
Copyright 2003 Wiley-Liss, Inc.
Publication Types:
PMID: 12616600 [PubMed - indexed for MEDLINE]
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Isoflavone aglycon produced by culture of soybean
extracts with basidiomycetes and its anti-angiogenic
activity.
Miura T,
Yuan L,
Sun B,
Fujii H,
Yoshida M,
Wakame K,
Kosuna K.
Department of Biochemistry, Amino Up Chemical Co., Ltd.,
363-32 Shin-ei, Kiyota-ku, Sapporo 004-0839, Japan.
au_labo@aminoup.co.jp
Soybean extracts (SBE) containing isoflavone glycosides
were cultured with Ganoderma lucidum mycelia producing
beta-glucosidase. The anti-angiogenic effects of the
cultivated product, containing rich in genistein, named
GCP (genistein combined polysaccharide), were assessed
with chick chorioallantoic membranes (CAM) and a mouse
dorsal air-sac model. Beta-glucosidase produced by the
mycelia converted the isoflavone glycosides into
aglycons. A test of volunteers showed that serum
concentrations of genistein in the subjects treated with
GCP (n = 4) at 3 h after administration were
significantly higher than those in the subjects treated
with SBE (n = 4). GCP inhibited angiogenesis in CAM, and
the activity of GCP was greater than that of SBE. GCP
inhibited the formation of new vessels induced by colon
carcinoma cells in vivo.
Publication Types:
PMID: 12596858 [PubMed - indexed for MEDLINE]
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A water-soluble extract from cultured medium of
Ganoderma lucidum (Rei-shi) mycelia suppresses
azoxymethane-induction of colon cancers in male F344
rats.
Lu H,
Kyo E,
Uesaka T,
Katoh O,
Watanabe H.
Department of Cellular Biology, Research Institute for
Radiation Biology and Medicine, Hiroshima University,
Hiroshima 734-8553, Japan.
The present study was designed to investigate the
protective effect of a dietary water-soluble extract
from cultured medium of Ganoderma lucidum (Rei-shi or
Mannentake) mycelia (designated as MAK) on the induction
and development of azoxymethane (AOM)-induced colon
tumors in male F344/Du Crj rats. A total of 80 animals
were divided into five groups at six weeks of age,
groups 2, 3 and 4 being given weekly subcutaneous
injections of AOM (15 mg/kg body weight) for the initial
3 weeks to induce colon tumors. Rats in group 1 and 5
were injected with the vehicle, 0.9% (w/v) saline,
following the same schedule. Rats in groups 1, 2, 3, 4
and 5 were fed MF, MF, 1.25% MAK, 2.5% MAK and 2.5% MAK
diets, respectively, starting 1 week before AOM
treatment and throughout the six-month experimental
period. There were no significant differences in number
of ACF, total AC and AC per site among groups 2 to 4,
but the tumor incidence was significantly lower, and
tumor size was smaller in group 4 (AOM + 2.5% MAK) than
in group 2 (AOM + MF). Additionally, beta-catenin
positive tumor cell nuclei were significantly decreased
in the MAK-fed rats (groups 3 and 4), which also
demonstrated lowering of the PCNA labeling index and a
shortened germinal region in the colon. The present
results thus indicate that dietary MAK could act as a
potent chemopreventive agent for colon carcinogenesis.
PMID: 12579275 [PubMed - indexed for MEDLINE]
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[Isolation, purification and bioactivities of exopoly
saccharides from fermented broth of Ganoderma lucidum]
[Article in Chinese]
Li P,
Zhang K.
School of Biotechnology, Wuxi University of Light
Industry, Wuxi 214036.
The exopolysaccharides of Ganoderma lucidum(GLEP)
extracted from the fermentation broth after removing
protein by Sevage and protease digestion procedures,
were applied to a column of DEAE-cellulose(OH- form),
and eluted stepwise with distilled water, sodium
hydrogen carbonate (0.1 mol/L, 0.3 mol/L, 0.5 mol/L
successively) and 0.1 mol/L sodium hydroxide. Five
fractions were obtained, and the main fraction was known
as GLEP-I, furthermore subjected to chromatography on a
column of SepharoseC1-6B, eluted at a flow rate of 30 mL/(cm2.h),
the relative viscosity of sample solution of 1.5. Two
fractions, GLEP-IFr1 and GLEP-IFr2 with a ratio of
3.8:1, were obtained. Molecular weight of GLEP-IFr1 and
GLEP-IFr2 was estimated to be 38,000 and 22,000 Dalton
respectively by Membrane Osmometer. The animal test
showed that GLEP-IFr1 could inhibited the growth of
Sarcoma 180 tumor in mice. The average inhibition ratio
was 57.4% (i.p. 10 mg/kg for 10 days). The result of
immunological activity showed that GLEP-IFr1 could
significantly improve macrophage cytophagy.
Publication Types:
PMID: 12548949 [PubMed - indexed for MEDLINE]
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Antitumor and antimetastatic effects on liver of
triterpenoid fractions of Ganoderma lucidum: mechanism
of action and isolation of an active substance.
Kimura Y,
Taniguchi M,
Baba K.
Second Department of Medical Biochemistry, School of
Medicine, Ehime University, Shigenobu-cho, Onsen-gun,
Ehime 791-095, Japan. yokim@m.ehimeu.ac.jp
The triterpenoid fraction (100 and 200 mg/kg) of the
fruit bodies of Ganoderma lucidum inhibited primary
solid-tumor growth in the spleen, liver metastasis and
secondary metastatic tumor growth in the liver in
intrasplenic Lewis lung carcinoma (LLC)-implanted mice.
In addition, the triterpenoid fraction (800 micrograms/mL)
inhibited angiogenesis induced by Matrigel (a soluble
basement membrane extract of the Engelbreth-Holm-Swam (EHS)
tumor) supplemented with vascular endothelial growth
factor (VEGF) and heparin in an in vivo model. This
suggested that the antitumor and antimetastatic
activities of the triterpenoid fraction of G. lucidum
might be due to the inhibition of tumor-induced
angiogenesis. Next, we attempted to isolate the active
substance(s) using the in vivo assay system of Matrigel-induced
angiogenesis. The acidic fraction of the triterpenoid
fraction inhibited the Matrigel-induced angiogenesis.
Compound I was isolated from the acidic fraction as an
active substance that inhibited the Martigel-induced
angiogenesis. Compound I was identified as ganoderic
acid F based on the data of IR, 1H- and 13C-NMR and MS
analyses.
PMID: 12530080 [PubMed - indexed for MEDLINE]
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Ganoderma lucidum suppresses motility of highly
invasive breast and prostate cancer cells.
Sliva D,
Labarrere C,
Slivova V,
Sedlak M,
Lloyd FP Jr,
Ho NW.
Cancer Research Laboratory, Methodist Research
Institute, 1800 N Capitol Avenue E504, Indianapolis, IN
46202, USA. dsliva@clarian.org
A dried powder from basidiomycetous fungi, Ganoderma
lucidum, has been used in East Asia in therapies for
several different diseases, including cancer. However,
the molecular mechanisms involved in the biological
actions of Ganoderma are not well understood. We have
recently demonstrated that phosphatidylinositol 3-kinase
(PI 3-kinase) and nuclear factor-kappaB (NF-kappaB)
regulate motility of highly invasive human breast cancer
cells by the secretion of urokinase-type plasminogen
activator (uPA). In this study, we investigated the
effect of G. lucidum on highly invasive breast and
prostate cancer cells. Here we show that spores or dried
fruiting body of G. lucidum inhibit constitutively
active transcription factors AP-1 and NF-kappaB in
breast MDA-MB-231 and prostate PC-3 cancer cells.
Furthermore, Ganoderma inhibition of expression of uPA
and uPA receptor (uPAR), as well secretion of uPA,
resulted in the suppression of the migration of
MDA-MB-231 and PC-3 cells. Our data suggest that spores
and unpurified fruiting body of G. lucidum inhibit
invasion of breast and prostate cancer cells by a common
mechanism and could have potential therapeutic use for
cancer treatment.
Publication Types:
PMID: 12408995 [PubMed - indexed for MEDLINE]
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Ganoderma lucidum extract induces cell cycle arrest
and apoptosis in MCF-7 human breast cancer cell.
Hu H,
Ahn NS,
Yang X,
Lee YS,
Kang KS.
Department of Veterinary Public Health, College of
Veterinary Medicine, Seoul National University, Sumon
441-744, Korea.
Although the pharmacology and clinical application of
water extracts of Ganoderma lucidum have been
extensively documented, little is known regarding its
alcohol extract. In the present study, the anti-tumor
effect of an alcohol extract of Ganoderma lucidum was
investigated using MCF-7 cells. We found that the
alcohol extract of Ganoderma lucidum inhibited cell
proliferation in a dose- and time-dependent manner,
which might be mediated through up-regulation of
p21/Waf1 and down-regulation of cyclin D1. Furthermore,
this compound can directly induce apoptosis in MCF-7
cells, which might be mediated through up-regulation of
a pro-apoptotic Bax protein and not by the immune
system. Our findings suggest that there are multiple
mechanisms underlying the anti-tumor effects of
Ganoderma lucidum. Copyright 2002 Wiley-Liss, Inc.
Publication Types:
PMID: 12397644 [PubMed - indexed for MEDLINE]
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Regression of prostate cancer following
administration of Genistein Combined Polysaccharide (GCP),
a nutritional supplement: a case report.
Ghafar MA,
Golliday E,
Bingham J,
Mansukhani MM,
Anastasiadis AG,
Katz AE.
Department of Urology, College of Physicians and
Surgeons of Columbia University, New York, NY, USA.
PURPOSE: It has been reported that genistein, an
isoflavone used in soybeans, has antiprostate cancer
effects. Genistein Combined Polysaccharide (GCP trade
mark; AMino Up, Sapporo, Japan), a nutritional
supplement manufactured in Japan, is composed of
genistein and a polysaccharide obtained from
basidiomycetes (mycelia) that grows in a variety of
mushrooms. METHODS: We report a case of a patient with a
biopsy proven prostate cancer showing clinical and
pathologic evidence of regression following
administration of GCP. The patient was enrolled in an
Institutional Review Board (IRB)-approved protocol and
received GCP for 6 weeks prior to radical prostatectomy.
RESULTS: The patient's prostate-specific antigen (PSA)
decreased from an initial value of 19.7 to 4.2 ng/mL
after 44 days of low-dose GCP. No cancer was identified
in the radical prostatectomy specimen and no side
effects were observed in this patient. CONCLUSION: This
case suggests that GCP, which has shown potent
inhibitory effects against prostate cancer in vitro, may
have some potential activity in the treatment and
prevention of prostate cancer.
Publication Types:
PMID: 12230910 [PubMed - indexed for MEDLINE]
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