Scientific Researches On:
Coriolus Versicolor (Yunzhi Mushroom)
USA National Center for Biotechnology Information
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1:
BMC Cancer. 2008 Mar 24;8:78.
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The immunomodulator PSK induces in vitro
cytotoxic activity in tumour cell lines via
arrest of cell cycle and induction of apoptosis.
Jiménez-Medina E,
Berruguilla E,
Romero I,
Algarra I,
Collado A,
Garrido F,
Garcia-Lora A.
Servicio de Análisis Clínicos e Inmunologia,
Hospital Universitario Virgen de las Nieves,
Universidad de Granada, Av, de las Fuerzas
Armadas 2, 18014 Granada, Spain. evajimenez@fundacionhvn.org
BACKGROUND: Protein-bound polysaccharide (PSK)
is derived from the CM-101 strain of the fungus
Coriolus versicolor and has shown anticancer
activity in vitro and in in vivo experimental
models and human cancers. Several randomized
clinical trials have demonstrated that PSK has
great potential in adjuvant cancer therapy, with
positive results in the adjuvant treatment of
gastric, esophageal, colorectal, breast and lung
cancers. These studies have suggested the
efficacy of PSK as an immunomodulator of
biological responses. The precise molecular
mechanisms responsible for its biological
activity have yet to be fully elucidated.
METHODS: The in vitro cytotoxic anti-tumour
activity of PSK has been evaluated in various
tumour cell lines derived from leukaemias,
melanomas, fibrosarcomas and cervix, lung,
pancreas and gastric cancers. Tumour cell
proliferation in vitro was measured by BrdU
incorporation and viable cell count. Effect of
PSK on human peripheral blood lymphocyte (PBL)
proliferation in vitro was also analyzed.
Studies of cell cycle and apoptosis were
performed in PSK-treated cells. RESULTS: PSK
showed in vitro inhibition of tumour cell
proliferation as measured by BrdU incorporation
and viable cell count. The inhibition ranged
from 22 to 84%. Inhibition mechanisms were
identified as cell cycle arrest, with cell
accumulation in G0/G1 phase and increase in
apoptosis and caspase-3 expression. These
results indicate that PSK has a direct cytotoxic
activity in vitro, inhibiting tumour cell
proliferation. In contrast, PSK shows a
synergistic effect with IL-2 that increases PBL
proliferation. CONCLUSION: These results
indicate that PSK has cytotoxic activity in
vitro on tumour cell lines. This new cytotoxic
activity of PSK on tumour cells is independent
of its previously described immunomodulatory
activity on NK cells.
Publication Types:
PMID: 18366723 [PubMed - indexed for MEDLINE]
PMCID: PMC2291471
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Anti-tumor effect of Coriolus versicolor
methanol extract against mouse B16 melanoma
cells: in vitro and in vivo study.
Harhaji Lj,
Mijatović S,
Maksimović-Ivanić D,
Stojanović I,
Momcilović M,
Maksimović V,
Tufegdzić S,
Marjanović Z,
Mostarica-Stojković M,
Vucinić Z,
Stosić-Grujicić S.
Department of Immunology, Institute for
Biological Research Sinisa Stanković, Belgrade
University, Belgrade, Serbia.
Numerous studies have shown immunostimulatory
and anti-tumor effects of water and standardized
aqueous ethanol extracts derived from the
medicinal mushroom, Coriolus versicolor, but the
biological activity of methanol extracts has not
been examined so far. In the present study we
investigated the anti-tumor effect of C.
versicolor methanol extract (which contains
terpenoids and polyphenols) on B16 mouse
melanoma cells both in vitro and in vivo.In
vitro treatment of the cells with the methanol
extract (25-1600 microg/ml) reduced melanoma
cell viability in a dose-dependent manner.
Furthermore, in the presence of the methanol
extract (200 microg/ml, concentration IC(50))
the proliferation of B16 cells was arrested in
the G(0)/G(1) phase of the cell cycle, followed
by both apoptotic and secondary necrotic cell
death. In vivo methanol extract treatment (i.p.
50 mg/kg, for 14 days) inhibited tumor growth in
C57BL/6 mice inoculated with syngeneic B16 tumor
cells. Moreover, peritoneal macrophages
collected 21 days after tumor implantation from
methanol extract-treated animals exerted
stronger tumoristatic activity ex vivo than
macrophages from control melanoma-bearing mice.
Taken together, our results demonstrate that C.
versicolor methanol extract exerts pronounced
anti-melanoma activity, both directly through
antiproliferative and cytotoxic effects on tumor
cells and indirectly through promotion of
macrophage anti-tumor activity.
Publication Types:
PMID: 18313195 [PubMed - indexed for MEDLINE]
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Polysaccharopeptide enhances the anticancer
activity of doxorubicin and etoposide on human
breast cancer cells ZR-75-30.
Wan JM,
Sit WH,
Louie JC.
Food and Nutritional Science Division, School of
Biological Sciences, The University of Hong
Kong, Hong Kong SAR, PR China. jmfwan@hkusua.hku.hk
In search of natural bioactive microbial
compounds with adjuvant properties, we have
previously showed that the polysaccharopeptide (PSP),
isolated from Chinese medicinal mushroom
Coriolus versicolor, was able to enhance the
cytotoxicity of certain S-phase targeted-drugs
on human leukemic HL-60 cells via some
cell-cycle and apoptotic-dependent pathways. The
present study aimed to investigate whether the
synergism of mechanisms of PSP with certain
chemotherapeutic drugs also applies to human
breast cancer. PSP treatment enhanced the
cytotoxicity of doxorubicin (Doxo), etoposide
(VP-16) but not cytarabine (Ara-C). Bivariate
bromodeoxyuridine (BrdUrd)/DNA flow cytometry
analysis estimated a longer DNA synthesis time
(Ts) for the PSP treated cancerous cells
suggesting that PSP enhanced the apoptotic
effect of Doxo and VP-16 via creating an S-phase
trap in the human breast cancer cell line
ZR-75-30. The participation of PSP in the
apoptotic machinery of the chemotherapeutic
agents was further supported by a reduced ratio
of protein expression of Bcl-xL/Bax of the
cancer cells. This study provides further
insight into the synergistic mechanisms of PSP
and supports the hypothesis that the anticancer
potentials of PSP is not limited to leukemia but
may also be used as an adjuvant therapy for
breast cancers.
Publication Types:
PMID: 18292947 [PubMed - indexed for MEDLINE]
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[Effect of Coriolus versicolor polysaccharide
B on membrane glycosaminoglycans and cellular
glutathione changes in RAW264.7 macrophages
exposed to angiotensin II]
[Article in Chinese]
Lou N,
Ma G,
Wang DF,
Zhu ZW,
Su QG,
Fang Y.
Intensive Care Unit, Sun Yat-sen University
Cancer Center, Guangzhou 510060, China. louning@mail.sysu.edu.cn
OBJECTIVE: To investigate the effect of Coriolus
versicolor polysaccharide B (CVP-B) on increased
membrane glycosaminoglycans (GAG) expression and
intracellular glutathione (GSH) of RAW264.7
macrophages exposed to angiotensin II (Ang II).
METHODS: The plasma membrane of RAW264.7
macrophages exposed to Ang II treatment was
isolated by ultracentrifugation, and the
membrane GAG expression was analyzed using 1,
9-dimethylmethylene blue (DMMB)
spectrophotometric assay for sulfated GAG. The
intracellular reduced GSH was determined using
fluorophotometry. RESULTS: The GAG content in
the macrophage membranes increased by up to 54%
following cell exposure to 1.0 micromol/L Ang
II, whereas in presence of 1.0 micromol;/L Ang
II, CVP-B at 1, 10, and 50 microg/ml decreased
the GAG content by 13%, 43% (P<0.01), and 52%
(P<0.01), respectively. The macrophage GSH
activity decreased by 69% following incubation
with 1.0 micromol;/L Ang II for 24 h, and CVP-B
treatment at 1, 10, and 50 microg/ml in presence
of 1.0 micromol;/L Ang II resulted in
significant increment of GSH activity by
31%(P<0.05), 104% (P<0.01), and 168% (P<0.01),
respectively. CONCLUSION: These data provide the
first evidence that CVP-B inhibits elevated GAG
expression in RAW264.7 macrophage membrane
induced by Ang II.
Publication Types:
PMID: 18158993 [PubMed - in process]
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Induction of cell cycle changes and
modulation of apoptogenic/anti-apoptotic and
extracellular signaling regulatory protein
expression by water extracts of I'm-Yunity (PSP).
Hsieh TC,
Wu P,
Park S,
Wu JM.
Department of Biochemistry & Molecular Biology,
New York Medical College, Valhalla, NY 10595,
USA. Tze-Chen_Hsieh@nymc.edu
BACKGROUND: I'm-Yunity (PSP) is a mushroom
extract derived from deep-layer cultivated
mycelia of the patented Cov-1 strain of Coriolus
versicolor (CV), which contains as its main
bioactive ingredient a family of polysaccharo-peptide
with heterogeneous charge properties and
molecular sizes. I'm-Yunity (PSP) is used as a
dietary supplement by cancer patients and by
individuals diagnosed with various chronic
diseases. Laboratory studies have shown that
I'm-Yunity (PSP) enhances immune functions and
also modulates cellular responses to external
challenges. Recently, I'm-Yunity (PSP) was also
reported to exert potent anti-tumorigenic
effects, evident by suppression of cell
proliferation and induction of apoptosis in
malignant cells. We investigate the mechanisms
by which I'm-Yunity (PSP) elicits these effects.
METHODS: Human leukemia HL-60 and U-937 cells
were incubated with increasing doses of aqueous
extracts of I'm-Yunity (PSP). Control and
treated cells were harvested at various times
and analyzed for changes in: (1) cell
proliferation and viability, (2) cell cycle
phase transition, (3) induction of apoptosis,
(4) expression of cell cycle, apoptogenic/anti-apoptotic,
and extracellular regulatory proteins. RESULTS:
Aqueous extracts of I'm-Yunity (PSP) inhibited
cell proliferation and induced apoptosis in
HL-60 and U-937 cells, accompanied by a cell
type-dependent disruption of the G1/S and G2/M
phases of cell cycle progression. A more
pronounced growth suppression was observed in
treated HL-60 cells, which was correlated with
time- and dose-dependent down regulation of the
retinoblastoma protein Rb, diminution in the
expression of anti-apoptotic proteins bcl-2 and
survivin, increase in apoptogenic proteins bax
and cytochrome c, and cleavage of poly(ADP-ribose)
polymerase (PARP) from its native 112-kDa form
to the 89-kDa truncated product. Moreover, I'm-Yunity
(PSP)-treated HL-60 cells also showed a
substantial decrease in p65 and to a lesser
degree p50 forms of transcription factor NF-kappaB,
which was accompanied by a reduction in the
expression of cyclooxygenase 2 (COX2). I'm-Yunity
(PSP) also elicited an increase in STAT1 (signal
transducer and activator of transcription) and
correspondingly, decrease in the expression of
activated form of ERK (extracellular
signal-regulated kinase). CONCLUSION: Aqueous
extracts of I'm-Yunity (PSP) induces cell cycle
arrest and alterations in the expression of
apoptogenic/anti-apoptotic and extracellular
signaling regulatory proteins in human leukemia
cells, the net result being suppression of
proliferation and increase in apoptosis. These
findings may contribute to the reported clinical
and overall health effects of I'm-Yunity (PSP).
Publication Types:
PMID: 16965632 [PubMed - indexed for MEDLINE]
PMCID: PMC1574346
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Coriolus versicolor (Yunzhi) extract
attenuates growth of human leukemia xenografts
and induces apoptosis through the mitochondrial
pathway.
Ho CY,
Kim CF,
Leung KN,
Fung KP,
Tse TF,
Chan H,
Lau CB.
School of Pharmacy, The Chinese University of
Hong Kong, Hong Kong, PR China.
Coriolus versicolor (CV), also called Yunzhi,
has been demonstrated to exert anti-tumor
effects on various types of cancer cells. Our
previous studies have demonstrated that a
standardized aqueous ethanol extract prepared
from CV inhibited the proliferation of human
leukemia cells via induction of apoptosis. The
present study aimed to evaluate the underlying
mechanisms of apoptosis through modulation of
Bax, Bcl-2 and cytochrome c protein expressions
in a human pro-myelocytic leukemia (HL-60) cell
line, as well as the potential of the CV extract
as anti-leukemia agent using the athymic mouse
xenograft model. Our results demonstrated that
the CV extract dose-dependently suppressed the
proliferation of HL-60 cells (IC50 = 150.6
microg/ml), with increased nucleosome production
from apoptotic cells. Expression of
pro-apoptotic protein Bax was significantly
up-regulated in HL-60 cells treated with the CV
extract, especially after 16 and 24 h.
Meanwhile, expression of anti-apoptotic protein
Bcl-2 was concomitantly down-regulated, as
reflected by the increased Bax/Bcl-2 ratio. The
CV extract markedly, but transiently, promoted
the release of cytochrome c from mitochondria to
cytosol after 24-h incubation. In vivo studies
in the athymic nude mouse xenograft model also
confirmed the growth-inhibitory activity of the
CV extract on human leukemia cells. In
conclusion, the CV extract attenuated the human
leukemia cell proliferation in vivo, and in
vitro possibly by inducing apoptosis through the
mitochondrial pathway. The CV extract is likely
to be valuable for the treatment of some forms
of human leukemia.
Publication Types:
PMID: 16865263 [PubMed - indexed for MEDLINE]
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Effects of VPS extract of Coriolus versicolor
on cancer of the large intestine using a serial
sacrifice technique.
Toth B,
Coles M,
Lynch J.
The Eppley Institute for Research in Cancer and
Allied Diseases and Department of Preventive and
Societal Medicine, University of Nebraska
Medical Center, Omaha, Nebraska 68198, USA.
btoth@unmc.edu
VPS, a hot water extract of the Coriolus
versicolor mushroom, was given at a 2% dose
level in the diet of female Swiss Webster CFW
outbred mice in a serial sacrifice experiment.
The mice were also administered either
1,2-dimethylhydrazine dihydrochloride (1,2-DMH)
as ten weekly subcutaneous (s.c) injections of
20 microg/g body weight or physiological saline
(PS) as ten weekly (s.c) injections of 0.01 ml/g
body weight. The animals were sacrificed at 26
weeks or 35 weeks after the first injection of
1,2-DMH or PS. The number of mice with large
intestinal tumors and the total number of these
tumors were: Group I (1,2-DMH), 29 and 438;
Group 2 (VPS + 1,2-DMH), 29 and 344; Group 3
(VPS + PS), 0 and 0; and Group 4 (PS), I and 1,
in the mice sacrificed at 26 weeks. The
corresponding tumor incidences in mice
sacrificed at 35 weeks were: Group 1 (1,2-DMH),
30 and 323; Group 2 (VPS + 1,2-DMH), 29 and 521;
Group 3 (VPS + PS), 1 and 2; and Group 4 (PS), 0
and 0. Histopathologically, the tumors were
diagnosed as polypoid adenomas and
adenocarcinomas of the cecum, colon and rectum.
Contrary to expectations, the VPS treatment
enhanced the development of large intestinal
tumors induced by 1,2-DMH in animals sacrificed
at 35 weeks after the first injection of the
carcinogen.
Publication Types:
PMID: 16724667 [PubMed - indexed for MEDLINE]
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Modulation of antipyrine clearance by
polysaccharide peptide (PSP) isolated from
Coriolus versicolor in the rat.
Chan SL,
Yeung JH.
Department of Pharmacology, Faculty of Medicine,
The Chinese University of Hong Kong, Shatin, N.T.,
Hong Kong SAR, China.
Polysaccharide peptide (PSP), isolated from
Coriolus versicolor COV-1, has been previously
shown to have immuno-stimulatory, anti-tumour
and analgesic effects in animal models. When
used as an adjunct in cancer chemotherapy in
clinical trials carried out in China, PSP
improved the quality of life in the patients by
improving appetite and alleviating symptoms
associated with cancer chemotherapy. In this
study, the effects of non-toxic doses of PSP on
phase I metabolism was investigated in the rat,
using the conventional probe antipyrine. Acute
PSP (3-5 micromol/kg, i.p.) treatment did not
produce significant changes in antipyrine
clearance. Sub-chronic treatment with PSP (1-3
micromol/kg/day, i.p., 3 days) decreased the
antipyrine clearance (30-35%), with an increase
in the plasma half-life (T1/2) by 55% and an
increase in the area under concentration-time
curve (AUC) by 61%. Total hepatic cytochrome
P450 (P450) was dose-dependently decreased
(32-54%) after sub-chronic, but not the acute
treatment of PSP. Given that PSP can affect
phase I metabolism and hepatic cytochrome P450
content, the concomitant use of PSP with other
therapeutic agents that undergo phase I
metabolism should be carefully monitored.
Publication Types:
PMID: 16698162 [PubMed - indexed for MEDLINE]
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Polysaccharide peptides from COV-1 strain of
Coriolus versicolor inhibit tolbutamide
4-hydroxylation in the rat in vitro and in vivo.
Yeung JH,
Chan SL,
Or PM.
Department of Pharmacology, Faculty of Medicine,
The Chinese University of Hong Kong, Shatin, NT,
Hong Kong, China. johnyeung@cuhk.edu.hk
Polysaccharide peptide (PSP), isolated from
COV-1 strain of Coriolus versicolor, is commonly
used as an adjunct in cancer chemotherapy in
China. In this study, the effects of whole PSP
extract and water extract of PSP on
4-hydroxylation of tolbutamide were investigated
in rat liver microsomes in vitro and in vivo in
the rat. Both the whole PSP extract and the
water soluble fraction (0.5-20 microM) decreased
the metabolism of tolbutamide to
4-hydroxytolbutamide in vitro. Enzyme kinetics
studies showed that PSP inhibited tolbutamide
4-hydroxylase activity in a competitive,
concentration-dependent manner. The whole PSP
extract had a Ki value of 12.6 microM and IC50
at 18.4 microM, while the water extract had a Ki
value of 6.9 microM and IC50 at 9.8 microM.
Sulphaphenazole, a specific human CYP2C9
inhibitor, showed a Ki value of 30.8 microM and
IC50 at 44.0 microM in the test system. In the
pharmacokinetic studies in vivo, acute PSP (4
micromol/kg, i.p.) treatment did not produce
significant changes in tolbutamide clearance,
but produced a decrease in the Cinitial (7.4%)
and an increase in the Vd (7.4%). Sub-chronic
pre-treatment of PSP (1-2 micromol/kg/day, i.p.)
for three days did not affect the clearance and
AUC of tolbutamide, but the Cinitial was
decreased, together with increases in the T1/2,
and Vd. The formation of 4-hydroxytolbutamide in
vivo was decreased in both acute and sub-chronic
studies. Taken together, this study demonstrated
the PSP can inhibit tolbutamide 4-hydroxylation
both in vitro and in vivo. Despite the fact that
CYP isoforms that metabolise tolbutamide are
different between rat and human liver due to
different catalytic characteristics, and rat
studies may not be directly extrapolatable to
man, the concomitant use of PSP with other CYP2C
substrates should be carefully monitored.
Publication Types:
PMID: 16698161 [PubMed - indexed for MEDLINE]
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Evaluation of cytotoxic and mutagenic effects
of Coriolus versicolor and Funalia trogii
extracts on mammalian cells.
Unyayar A,
Demirbilek M,
Turkoglu M,
Celik A,
Mazmanci MA,
Erkurt EA,
Unyayar S,
Cekic O,
Atacag H.
Department of Environmental Engineering, Mersin
University, Mersin, Turkey. aunyayar@mersin.edu.tr
This study examined the in vitro cytotoxic
activities of standardized aqueous bioactive
extracts prepared from Coriolus versicolor and
Funalia trogiiATCC 200800 on HeLa and fibroblast
cell lines using a MTT
(3-[4,5-dimetiltiazol-2-]-2-5-difeniltetrazolium
bromide) cytotoxicity assay. F. trogii and C.
versicolor extracts were cytotoxic to both cell
lines. At 10 microL treatment level, F. trogii
and C. versicolor extracts inhibited
proliferation of HeLa cancer cells by 71.5% and
45%, respectively, compared with controls.
Toxicity was lower toward normal fibroblasts. In
the latter case, treatment at 10 microL level
with F. trogii and C. versicolor extracts
reduced cell proliferation by 51.3% and 38.7%,
respectively. In separate experiments, the
mitotic index (MI) obtained with 3 microL
treatment level of unheated extracts of the two
fungi was comparable to the MI value obtained by
treatment with 4 microg/mL MMC (anticancer agent
mitomycin-C). A significant induction of sister
chromatid exchange (SCE) was observed in normal
cultured lymphocytes treated with MMC (4 microg/mL).
MMC treatment reduced replication index compared
with treatment with unheated F. trogii extract
and negative controls (p < 0.001). In contrast
to MMC, F. trogii extracts did not affect the
proliferation of human lymphocytes compared with
controls (p > 0.05). Laccase and peroxidase
enzyme activities in F. trogii extract were
implicated in their inhibitory effect on cancer
cells. F. trogii extract was concluded to have
antitumor activity.
PMID: 16455591 [PubMed - indexed for MEDLINE]
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Polysaccharide peptides from COV-1 strain of
Coriolus versicolor induce hyperalgesia via
inflammatory mediator release in the mouse.
Chan SL,
Yeung JH.
Department of Pharmacology, Faculty of Medicine,
Basic Medical Sciences Building, The Chinese
University of Hong Kong, Shatin, N.T., Hong Kong
SAR, China.
Polysaccharide peptide (PSP), isolated from
Coriolus versicolor COV-1, has been widely used
as an adjunct to cancer chemotherapy and as an
immuno-stimulator in China. In this study, the
anti-nociceptive effects of PSP were
investigated in two different pain models in the
mouse. In the acetic acid-induced writhing
model, initial studies showed that PSP decreased
the number of acetic acid-induced writhing by
92.9%, which, by definition, would constitute an
analgesic effect. However, further studies
showed that PSP itself induced a dose-dependent
writhing response. Studies on inflammatory
mediator release showed that PSP increased the
release of prostaglandin E2, tumor necrosis
factor-alpha, interleukin-1beta, and histamine
in mouse peritoneal macrophages and mast cells
both in vitro and in vivo. The role of
inflammatory mediator release in PSP-induced
writhing was confirmed when diclofenac and
dexamethasone decreased the number of writhing
responses by 54% and 58.5%, respectively.
Diphenhydramine totally inhibited the PSP-induced
writhing. In the hot-plate test, PSP
dose-dependently shortened the hind paw
withdrawal latency, indicative of a hyperalgesic
effect. The hyperalgesic effect was reduced by
pretreatment with the anti-inflammatory drugs.
In conclusion, the PSP-induced hyperalgesia was
related to activation of peritoneal resident
cells and an increase in the release of
inflammatory mediators.
Publication Types:
PMID: 16310221 [PubMed - indexed for MEDLINE]
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Effects of polysaccharide peptide (PSP) from
Coriolus versicolor on the pharmacokinetics of
cyclophosphamide in the rat and cytotoxicity in
HepG2 cells.
Chan SL,
Yeung JH.
Department of Pharmacology, Faculty of Medicine,
The Chinese University of Hong Kong, Shatin, N.T.,
Hong Kong SAR, China. cslkel@hotmail.com
Polysaccharide peptide (PSP), isolated from
Coriolus versicolor COV-1, has been shown to
restore the immunological effects against
cyclophosphamide-induced immuno-suppression,
although the mechanism(s) involved remain
uncertain. This study investigated the
PSP-cyclophosphamide interaction by studying the
effects of PSP on the pharmacokinetic of
cyclophosphamide in the rat and the effect of
PSP on the cytotoxic effects of cyclophosphamide
on a cancer cell line (HepG2 cells). In the
pharmacokinetic studies in the rat, acute
pre-treatment of PSP (4 micromol/kg/day, i.p.)
decreased the clearance (CL) of cyclophosphamide
by 31%, with a concomitant increase in the area
under concentration-time curve (AUC) by 44%, and
prolongation of the plasma half-life (T(1/2)) by
43%. Sub-chronic pre-treatment of PSP (2
micromol/kg/day, i.p., 3 days) decreased the CL
of cyclophosphamide by 33%, with a concomitant
increase in the AUC by 50%, and prolongation of
the plasma T(1/2) by 34%. In cytotoxicity
studies using HepG2 cells, non-toxic dose of PSP
(1-10 microM) enhanced the cytotoxicity of
cyclophosphamide. PSP at 10 microM further
decreased HepG2 cell viability by 22% compared
to when cyclophosphamide was present alone. In
summary, PSP enhanced the cytotoxic effect of
cyclophosphamide on a cancer cell line in vitro
and altered the pharmacokinetics of
cyclophosphamide in vivo in the rat. Both of
these effects may be beneficial in the use of
PSP as an adjunct to cyclophosphamide treatment.
Publication Types:
PMID: 16297519 [PubMed - indexed for MEDLINE]
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Lack of prevention of large intestinal cancer
by VPS, an extract of Coriolus versicolor
mushroom.
Coles M,
Toth B.
Eppley Institute, University of Nebraska Medical
Center, Omaha, NE 68198, USA.
Cancer prevention studies were conducted with
VPS, a hot water extract of the Coriolus
versicolor (CV) mushroom, in female Swiss mice.
The extract was administered in the diet for
life to the animals. Three groups of mice
received the following treatments: a).
1,2-dimethylhydrazine dihydrochloride (1,2-DMH)
was administered as 10 weekly subcutaneous
injections of 20 microg/g body weight, starting
at 9 weeks of age; b). VPS was given at a 2%
dose level starting at 7 weeks of age followed
by 1,2-DMH, as described in group a; c). 1,2-DMH
was administered as described in group a
followed by VPS at a 2% dose level starting at
21 weeks of age. The number of animals with
large intestinal tumors and the total number of
these tumors were: a). 30,321; b). 29,359; and
c). 28,415. These differences are not
statistically significant. Because extracts of
the CV mushroom are used by cancer patients as
nutritional supplements in the U.S., and
particularly in the Orient, the present negative
result should caution its users.
Publication Types:
PMID: 16097440 [PubMed - indexed for MEDLINE]
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Immunomodulatory activities of Yunzhi and
Danshen in post-treatment breast cancer
patients.
Wong CK,
Bao YX,
Wong EL,
Leung PC,
Fung KP,
Lam CW.
Department of Chemical Pathology, The Chinese
University of Hong Kong, Prince of Wales
Hospital, Shatin, Hong Kong, PR. China.
Breast cancer is the most common cancer among
women worldwide. Discomfort and fatigue are
usually arisen from anticancer therapy such as
surgery, radiotherapy, chemotherapy, hormonal
therapy, or combination therapy, because of the
suppressed immunological functions. Yunzhi (Coriolus
versicolor) can modulate various immunological
functions in vitro, in vivo, and in human
clinical trials. Danshen (Salvia miltiorrhiza)
has been shown to benefit the circulatory system
by its vasodilating and anti-dementia activity.
The purpose of this clinical trial was to
evaluate the immunomodulatory effects of
Yunzhi-Danshen capsules in post-treatment breast
cancer patients. Eighty-two patients with breast
cancer were recruited to take Yunzhi [50 mg/kg
body weight, 100% polysaccharopeptide (PSP)] and
Danshen (20 mg/kg body weight) capsules every
day for a total of 6 months. EDTA blood samples
were collected every 2 months for the
investigation of immunological functions. Flow
cytometry was used to assess the percentages and
absolute counts of human lymphocyte subsets in
whole blood. Plasma level of soluble
interleukin-2 receptor (sIL-2R) was measured by
enzyme-linked immunosorbent assay (ELISA).
Results showed that the absolute counts of
T-helper lymphocytes (CD4+), the ratio of
T-helper (CD4+)/T suppressor and cytotoxic
lymphocytes (CD8+), and the percentage and the
absolute counts of B-lymphocytes were
significantly elevated in patients with breast
cancer after taking Yunzhi-Danshen capsules,
while plasma slL-2R concentration was
significantly decreased (all p < 0.05).
Therefore, the regular oral consumption of
Yunzhi-Danshen capsules could be beneficial for
promoting immunological function in
post-treatment of breast cancer patients.
Publication Types:
PMID: 16047556 [PubMed - indexed for MEDLINE]
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Molecular characterization of Coriolus
versicolor PSP-induced apoptosis in human
promyelotic leukemic HL-60 cells using cDNA
microarray.
Zeng F,
Hon CC,
Sit WH,
Chow KY,
Hui RK,
Law IK,
Ng VW,
Yang XT,
Leung FC,
Wan JM.
Department of Zoology, The University of Hong
Kong, Hong Kong, SAR, P.R. China.
Proteins and peptide bound polysaccharides (PSP)
extracted from Basidiomycetous fungi are widely
used in cancer immunotherapy and recently
demonstrated to induce apoptosis in cancer cells
in vitro. In order to provide the molecular
pharmacological mechanisms of PSP on human
cancer cells, we investigated the gene
expression profiles of PSP-treated apoptotic
human promyelotic leukemic HL-60 cells using
ResGen 40k IMAGE printed cDNA microarray. In
total 378 and 111 transcripts were identified as
differentially expressed in the apoptotic cells
by at least a factor of 2 or 3, respectively.
Our data show that PSP-induced apoptosis in
HL-60 cells might be mediated by up-regulation
of early transcription factors such as AP-1,
EGR1, IER2 and IER5, and down-regulation of NF-kappaB
transcription pathways. Other gene expression
changes, including the increase of several
apoptotic or anti-proliferation genes, such as
GADD45A/B and TUSC2, and the decrease of a batch
of phosphatase and kinase genes, may also
provide further evidences in supporting the
process of PSP induced apoptosis in cancer
cells. Some of the well-characterized
carcinogenesis-related gene transcripts such as
SAT, DCT, Melan-A, uPA and cyclin E1 were also
alternated by PSP in the HL-60 cells. These
transcripts can be employed as markers for
quality control of PSP products on functional
levels. The present study provides new insight
into the molecular mechanisms involved in PSP-induced
apoptosis in leukemic HL-60 cells analyzed by
cDNA microarray.
Publication Types:
PMID: 16010435 [PubMed - indexed for MEDLINE]
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Induction of S phase cell arrest and caspase
activation by polysaccharide peptide isolated
from Coriolus versicolor enhanced the cell cycle
dependent activity and apoptotic cell death of
doxorubicin and etoposide, but not cytarabine in
HL-60 cells.
Hui KP,
Sit WH,
Wan JM.
Department of Zoology, The University of Hong
Kong, Pokfulam Road, Hong Kong, SAR, P.R. China.
Activation of the cell death program (apoptosis)
is a strategy for the treatment of human cancer,
and unfortunately a large number of drugs
identified as cell cycle-specific agents for
killing cancer cells are also toxic to normal
cells. The present study demonstrates that the
polysaccharide peptide (PSP) extracted from the
Chinese medicinal mushroom, Coriolus versicolor,
used in combination therapy in China, has the
ability to lower the cytotoxicity of certain
anti-leukemic drugs via their interaction with
cell cycle-dependent and apoptotic pathways.
Flow cytometry analysis demonstrated that
pre-treatment of PSP (25-100 microg/ml)
dose-dependently enhanced the cell cycle
perturbation and apoptotic activity of
doxorubicin (Doxo) and etoposide (VP-16), but
not cytarabine (Ara-C) in human promyelocytic
leukemia HL-60 cells. The antagonistic result
from combined treatment with Ara-C and PSP may
be caused by the removal of HL-60 cells in the
G1-S boundary by PSP before exposure to Ara-C. A
negative correlation between the increase in
apoptotic cell population (pre-G1 peak) with the
S-phase cell population expression (R2=0.998),
the expression of cyclin E expression (R2=0.872)
and caspase 3 activity (R2=0.997) suggests that
PSP enhanced the apoptotic machinery of Doxo and
VP-16 in a cell cycle-dependent manner and is
mediated, at least in part, by the PSP-mediated
modulation of the regulatory checkpoint cyclin E
and caspase 3. This study is the first to
describe the cell cycle mechanistic action of
PSP and its interaction with other anticancer
agents. Our data support the potential
development of PSP as an adjuvant for leukemia
treatment, but also imply the importance of
understanding its interaction with individual
anticancer agents.
Publication Types:
PMID: 15944782 [PubMed - indexed for MEDLINE]
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Differential anti-tumor activity of coriolus
versicolor (Yunzhi) extract through p53- and/or
Bcl-2-dependent apoptotic pathway in human
breast cancer cells.
Ho CY,
Kim CF,
Leung KN,
Fung KP,
Tse TF,
Chan H,
Lau CB.
School of Pharmacy, The Chinese University of
Hong Kong, Shatin, New Territories, Hong Kong.
Coriolus versicolor (CV), also called Yunzhi,
has been demonstrated to exert anti-tumor
effects on various types of cancer cells, but
the underlying mechanism has not been fully
elucidated. The present study aimed to evaluate
the in vitro anti-tumor activity of a
standardized aqueous ethanol extract prepared
from CV on four breast cancer cell lines using
MTT assay, and test whether the mechanism
involves apoptosis induction and modulation of
p53 and Bcl-2 protein expressions using cell
death detection ELISA, p53 and Bcl-2 ELISAs
respectively. Our results demonstrated that the
CV extract dose-dependently suppressed the
proliferation of three breast tumor cell lines,
with ascending order of IC50 values: T-47D,
MCF-7, MDA-MB-231, while BT-20 cells were not
significantly affected. Tumoricidal activity of
the CV extract was found to be comparable to a
chemotherapeutic anti-cancer drug, mitomycin C.
Nucleosome productions in apoptotic MDA-MB-231,
MCF-7 and T-47D cells were significantly
augmented in a time-dependent manner and
paralleled the anti-proliferative activity of CV
extract. Expression of p53 protein was
significantly upregulated only in T-47D cells
treated with the CV extract in a dose- and
time-dependent fashion, but not in MCF-7 (except
at 400 mug/ml after 16 h) and MDA-MB-231 cells.
The CV extract significantly induced a
dose-dependent downregulation of Bcl-2 protein
expression in MCF-7 and T-47D cells, but not in
MDA-MB-231 cells. These results suggested that
apoptosis induction, differentially dependent of
p53 and Bcl-2 expressions, might be the possible
mechanism of CV extract-mediated cytotoxicity in
human breast cancer cells in vitro.
Publication Types:
PMID: 15908782 [PubMed - indexed for MEDLINE]
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The cell death process of the anticancer
agent polysaccharide-peptide (PSP) in human
promyelocytic leukemic HL-60 cells.
Yang X,
Sit WH,
Chan DK,
Wan JM.
Department of Zoology, The University of Hong
Kong, Pokfalum Road, Hong Kong, SAR, P.R. China.
The polysaccharide peptide (PSP) isolated from
the mycelia of Chinese Medicinal fungus Coriolus
versicolor has proven benefits in clinical
trials in China but the mechanism of action has
not been elucidated. In this study, HL-60 cell
line was used to investigate the
anti-proliferation and cell death process of PSP.
The cytotoxicity of PSP on normal human
T-lymphocytes was also evaluated. We show that
PSP induced apoptosis of human promyelocytic
leukemia HL-60 cells but not of normal human
T-lymphocytes. The apoptotic machinery induced
by PSP was associated with a decrease in Bcl-2/Bax
ratio, drop in mitochondrial transmembrane
potential, cytochrome c release, and activation
of caspase-3, -8 and -9. Activation of the
cellular apoptotic program is a current strategy
for the treatment of human cancer, and the
selectivity of PSP to induce apoptosis in
cancerous and not on normal cells supports its
development as a novel anticancer agent.
Publication Types:
PMID: 15870943 [PubMed - indexed for MEDLINE]
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Treatment of cancer with mushroom products.
Monro JA.
Breakspear Hospital, Hemel Hempstead, Herts,
United Kingdom. jmonro@breakspearmedical.com
Cancer has been attributed to 3 causes:
pollution, infection, and poor nutrition.
Conventional treatments include surgery,
chemotherapy, and radiotherapy. The author
proposes that immunotherapy also be considered.
Among other environmental influences, dietary
deficiencies and carcinogenic viral infections
must be investigated and treated wherever
possible. It has been suggested that mushrooms,
in particular, have a structure that is
immunomodulatory because it resembles the
proteoglycan structure in the human
extracellular matrix, and both are metabolically
active. Inasmuch as mitochondria have a
bacterial origin, proteoglycans may have a
mushroom origin. The author describes a study
which shows that natural killer cells can double
in number with 8 wk of treatment with Coriolus
versicolor. Also described is an epidemiological
survey of cancer deaths among Flammulina
velutipes farmers in Japan, which found that the
mushroom farmers had lower rates of cancer
deaths than controls who were not involved in
mushroom farming.
Publication Types:
PMID: 15259434 [PubMed - indexed for MEDLINE]
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Fungal polysaccharopeptide inhibits tumor
angiogenesis and tumor growth in mice.
Ho JC,
Konerding MA,
Gaumann A,
Groth M,
Liu WK.
Department of Anatomy, Faculty of Medicine, The
Chinese University of Hong Kong, Shatin, New
Territories, Hong Kong, China.
Angiogenesis is crucial to tumor growth and
metastasis, and interruption of this process is
a prime avenue for therapeutic intervention of
tumor proliferation. The present study has made
use of the S180 tumor-bearing mouse model to
investigate the polysaccharopeptide, PSP,
isolated from the edible mushroom Coriolus
versicolor, a herbal medicine known for its
anti-angiogenesis properties. Quantitative
analysis of microcorrosion casting of the tumor
tissue showed more angiogenic features such as
dense sinusoids and hot spots, in control
(untreated) than in PSP-treated animals.
Immunostaining of tumor tissues with antibody
against the endothelial cell marker (Factor
VIII) demonstrated a positive correlation in
that both the vascular density and tumor weight
were lower in mice treated with PSP.
Morphometric analysis of corrosion casts
revealed that, even though the total amount of
new vessel production was reduced, the basic
tumor type-specific vascular architecture was
retained. However, the expression of vascular
endothelial cell growth factor (VEGF) in these
tumors was suppressed. In conclusion,
anti-angiogenesis should be one of the pathways
through which PSP mediated its anti-tumor
activity.
Publication Types:
PMID: 15234192 [PubMed - indexed for MEDLINE]
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