Scientific Researches On:
Coriolus Versicolor (Yunzhi Mushroom)
USA National Center for Biotechnology Information
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21:
Life Sci. 2004 Jul 2;75(7):797-808.
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Cytotoxic activities of Coriolus versicolor (Yunzhi)
extract on human leukemia and lymphoma cells by
induction of apoptosis.
Lau CB,
Ho CY,
Kim CF,
Leung KN,
Fung KP,
Tse TF,
Chan HH,
Chow MS.
School of Pharmacy, The Chinese University of Hong Kong,
Shatin, New Territories, Hong Kong. claralau@cuhk.edu.hk
Coriolus versicolor (CV), also known as Yunzhi, is one
of the commonly used Chinese medicinal herbs. Although
recent studies have demonstrated its antitumour
activities on cancer cells in vitro and in vivo, the
exact mechanism is not fully elucidated. Hence, the
objective of this study was to examine the in vitro
cytotoxic activities of a standardized aqueous ethanol
extract prepared from Coriolus versicolor on a B-cell
lymphoma (Raji) and two human promyelocytic leukemia
(HL-60, NB-4) cell lines using a MTT cytotoxicity assay,
and to test whether the mechanism involves induction of
apoptosis. Cell death ELISA was employed to quantify the
nucleosome production resulting from nuclear DNA
fragmentation during apoptosis. The present results
demonstrated that CV extract at 50 to 800 microg/ml
dose-dependently suppressed the proliferation of Raji,
NB-4, and HL-60 cells by more than 90% (p < 0.01), with
ascending order of IC50 values: HL-60 (147.3 +/- 15.2
microg/ml), Raji (253.8 +/- 60.7 microg/ml) and NB-4
(269.3 +/- 12.4 microg/ml). The extract however did not
exert any significant cytotoxic effect on normal liver
cell line WRL (IC50 > 800 microg/ml) when compared with
a chemotherapeutic anticancer drug, mitomycin C (MMC),
confirming the tumour-selective cytotoxicity. Nucleosome
productions in HL-60, NB-4 and Raji cells were
significantly increased by 3.6-, 3.6- and 5.6-fold
respectively upon the treatment of CV extract, while no
significant nucleosome production was detected in
extract-treated WRL cells. The CV extract was found to
selectively and dose-dependently inhibit the
proliferation of lymphoma and leukemic cells possibly
via an apoptosis-dependent pathway. Copyright 2004
Elsevier Inc.
Publication Types:
PMID: 15183073 [PubMed - indexed for MEDLINE]
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Effect of PSK on the maturation of dendritic cells
derived from human peripheral blood monocytes.
Kanazawa M,
Mori Y,
Yoshihara K,
Iwadate M,
Suzuki S,
Endoh Y,
Ohki S,
Takita K,
Sekikawa K,
Takenoshita S.
Department of Surgery II, Fukushima Medical University,
1 Hikarigaoka, Fukushima City, 960-1295, Japan. kanazawa@cc.fmu.ac.jp
Dendritic cells (DCs) are powerful antigen-presenting
cells (APCs) that have attracted attention in recent
years from the viewpoint of DC vaccine therapy against
cancer. However, the existence of a strongly
immunosuppressed state in cancer-bearing individuals
inhibits DC maturation, which is one of the problems
facing anti-cancer DC vaccine therapy. Protein-bound
polysaccharide K (PSK), which is extracted from the
cultured mycelium of Coriolus versicolor (Fr.) Quél, is
used as an anti-cancer agent in Japan. PSK is reported
to improve the immunosuppressed state and might be
associated with DC maturation directly. We examined the
effect of PSK on the maturation of DC derived from
CD14-positive cells obtained from human peripheral blood
monocytes using a negative selection method.
CD14-positive cells cultured in the presence of PSK
significantly increased the expression of HLA class II
antigen and CD40; significantly increased the number and
expression of CD80-, CD86- and CD83-positive cells;
decreased Fluorescein isothiocyanate (FITC)-dextran
uptake, augmented IL-12 production; augmented the
allogeneic mixed lymphocyte reaction; and induced
antigen-specific cytotoxicity. These results indicate
that PSK promotes both the phenotypic and functional
maturation of DC derived from human CD14-positive
mononuclear cells. The clinical significance of the
combined use of PSK in DC vaccine therapy remains for
study.
PMID: 15019294 [PubMed - indexed for MEDLINE]
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Polysaccharopeptides of Coriolus versicolor:
physiological activity, uses, and production.
Cui J,
Chisti Y.
Institute of Technology and Engineering PN456, Massey
University, Private Bag 11 222, 5320, Palmerston North,
New Zealand.
The protein-bound polysaccharides or
polysaccharopeptides produced by Coriolus versicolor are
effective immunopotentiators, which are used to
supplement the chemotherapy and radiotherapy of cancers
and various infectious diseases. Antitumor activity of
polysaccharopeptides has been documented. Several kinds
of protein-bound polysaccharides have been shown to be
produced by the white rot fungus, C. versicolor.
Although some of these polymers are structurally
distinct, they are not distinguishable in terms of their
physiological activity. This review focuses on the
physiologically active polysaccharopeptides of C.
versicolor. In nature, C. versicolor occurs as a
mushroom body, but the fungus can be grown as mycelial
biomass in submerged culture in bioreactors. Mushrooms
gathered in the wild, cultivated mushrooms, and the
mycelial biomass of submerged culture are used to
produce the polysaccharopeptides. Submerged cultures are
typically carried out in batches lasting 5-7 days and at
25-27 degrees C. Hot water extraction of the biomass is
used to recover the thermostable polysaccharopeptides
that are concentrated, purified, and dried into a powder
for medicinal use. In view of the documented
physiological benefits of these compounds, extensive
research is underway on the structure, composition,
production methods, and use of new C. versicolor strains
for producing the therapeutic biopolymers. Properties,
physiological activity, recovery, and purification of
the bioactive polysaccharopeptides are discussed.
Publication Types:
PMID: 14499133 [PubMed - indexed for MEDLINE]
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Coriolus versicolor polysaccharide peptide slows
progression of advanced non-small cell lung cancer.
Tsang KW,
Lam CL,
Yan C,
Mak JC,
Ooi GC,
Ho JC,
Lam B,
Man R,
Sham JS,
Lam WK.
Department of Medicine, The University of Hong Kong,
Queen Mary Hospital, Pokfulam, Hong Kong SAR, China.
kwttsang@hku.hk
BACKGROUND: Non-small cell lung cancer (NSCLC) is a
leading cause of cancer deaths, and over 60% of patients
present with advanced stages. Although polysaccharide
peptides (PSP), isolated from the fungus Coriolus
versicolor, have been reported to have anti-tumor
effects, its clinical efficacy has not been properly
evaluated. METHODS: Double-blind placebo-controlled
randomized study to evaluate the effects of 28-day
administration of PSP (Windsor Pharmaceutical, Hong
Kong) on patients, who had completed conventional
treatment for advanced NSCLC. RESULTS: Thirty-four
patients, with no significant difference in their
baseline demographic, clinical or tumor characteristics,
or previous treatment regimes (P>0.05) were recruited
into each of the PSP and control arms. After 28-day
treatment, there was a significant improvement in blood
leukocyte and neutrophil counts, serum IgG and IgM, and
percent of body fat among the PSP, but not the control,
patients (P<0.05). Although the evaluable PSP patients
did not improve in NSCLC-related symptoms, there were
significantly less PSP patients withdrawn due to disease
progression, than their control counterparts (5.9 and
23.5%, respectively; P=0.04; OR 4.00). There was no
reported adverse reaction attributable to the trial
medications. CONCLUSION: PSP treatment appears to be
associated with slower deterioration in patients with
advanced NSCLC.
Publication Types:
PMID: 12814145 [PubMed - indexed for MEDLINE]
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Coriolus versicolor: a medicinal mushroom with
promising immunotherapeutic values.
Chu KK,
Ho SS,
Chow AH.
School of Pharmacy, Faculty of Medicine, Chinese
University of Hong Kong, Shatin, NT.
Coriolus versicolor (CV) is a medicinal mushroom widely
prescribed for the prophylaxis and treatment of cancer
and infection in China. In recent years, it has been
extensively demonstrated both preclinically and
clinically that aqueous extracts obtained from CV
display a wide array of biological activities, including
stimulatory effects on different immune cells and
inhibition of cancer growth. The growing popularity of
aqueous CV extracts as an adjunct medical modality to
conventional cancer therapies has generated substantial
commercial interest in developing these extracts into
consistent and efficacious oral proprietary products.
While very limited information is available on the
physical, chemical, and pharmacodynamic properties of
the active principles present in these extracts, there
has been sufficient scientific evidence to support the
feasibility of developing at least some of these
constituents into an evidence-based immunodulatory
agent. In this article, the background, traditional
usage, pharmacological activities, clinical effects,
adverse reactions, active constituents, and regulatory
aspects of CV are reviewed. Presented also in this
review are the current uses and administration,
potential drug interactions, and contraindication of
aqueous extracts prepared from CV.
Publication Types:
PMID: 12211223 [PubMed - indexed for MEDLINE]
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Biological activity of 4-acetyltropolone, the minor
component of Thujopsis dolabrata SIeb. et Zucc. hondai
Mak.
Morita Y,
Matsumura E,
Tsujibo H,
Yasuda M,
Okabe T,
Sakagami Y,
Kumeda Y,
Ishida N,
Inamor Y.
Osaka Organic Chemical Industry, Ltd, Kashiwara, Japan.
4-Acetyltropolone, a minor component of Thujopsis
dolabrata SIEB. et Zucc. hondai MAKINO, showed
antimicrobial activity against various microorganisms
including wood-rotting fungi, a phytogrowth-inhibitory
effect with chlorophyll biosynthesis inhibition,
cytotoxic effect and inhibitory activity on
metalloproteases. This compound had strong antifungal
activity on Daedalea dickinsii IFO-4979 [minimum
inhibitory concentration (MIC): 0.2 microg/ml] and
Coriolus versicolor IFO-4940 (MIC: 0.39 microg/ml). Its
cytotoxic effect at 20.0/microg/ml on human stomach
cancer KATO-III and Ehrich's ascites carcinoma was
stronger than those of podophyllotoxin, vincristine and
vinblastine, the anticancer agents isolated from higher
plants and used clinically. This compound also had
potent antibacterial activity against Staphylococcus
epidermidis IFO-12993, its MIC being 1.56 microg/ml.
However, other biological activities of
4-acetyltropolone were lower than those of hinokitiol
which is the main component of this plant, suggesting
that the contribution of the acetyl group at C-4 to
biological activity is smaller than that of the
isopropyl group at that position. The acute toxicity of
4-acetyltropolone (LD50: 335.2 mg/kg) to mice was much
lower than that of hinokitiol (LD50: 191 mg/kg).
Publication Types:
PMID: 12186430 [PubMed - indexed for MEDLINE]
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Anticancer effects and mechanisms of polysaccharide-K
(PSK): implications of cancer immunotherapy.
Fisher M,
Yang LX.
Radiobiology Laboratory, St. Mary's Medical Center,
California Pacific Medical Center Research Institute,
San Francisco 94118, USA.
Polysaccharide-K (polysaccharide-Kureha; PSK), also
known as krestin, is a unique protein-bound
polysaccharide, which has been used as a
chemoimmunotherapy agent in the treatment of cancer in
Asia for over 30 years. PSK and Polysaccharopeptide (PSP)
are both protein-bound polysaccharides which are derived
from the CM-101 and COV-1 strains of the fungus Coriolus
versicolor by Japanese and Chinese researchers,
respectively. Both polysaccharide preparations have
documented anticancer activity in vitro, in vivo and in
human clinical trials, though PSK has been researched
longer and has therefore undergone more thorough
laboratory, animal and clinical testing. Several
randomized clinical trials have demonstrated that PSK
has great potential as an adjuvant cancer therapy agent,
with positive results seen in the adjuvant treatment of
gastric, esophageal, colorectal, breast and lung
cancers. These studies have suggested the efficacy of
PSK as an immunotherapy or biological response modifier
(BRM). BRMs potentially have the ability to improve the
"host versus tumor response," thereby increasing the
ability of the host to defend itself from tumor
progression. The mechanisms of biological response
modification by PSK have yet to be clearly and
completely elucidated. Some studies suggest that PSK may
act to increase leukocyte activation and response
through up-regulation of key cytokines. Indeed, natural
killer (NK) and lymphocyte-activated killer (LAK) cell
activation has been demonstrated in vivo and in vitro,
and recent genetic studies reveal increased expression
of key immune cytokines in response to treatment with
PSK. An antimetastatic action of PSK has also been
demonstrated and is perhaps attributed to its potential
to inhibit metalloproteinases and other enzymes involved
in metastatic activity. PSK has also been shown to cause
differentiation of leukemic cells in vitro, and this
effect has been attributed to induction of
differentiation cytokines. PSK has further been shown to
have antioxidant capacity which may allow it to play a
role as a normal tissue chemo- and radio-protector when
used in combination with adjuvant or definitive
chemotherapy and/or radiotherapy in the treatment of
cancer, while it may also enable it to defend the host
from oxidative stress. Interestingly, studies have also
shown that PSK may actually inhibit carcinogenesis by
inhibiting the action of various carcinogens on
vulnerable cell lines. This action of PSK may play a
role in preventing second primary tumors when an
inducing agent, such as tobacco or asbestos, is
suspected and may also prevent second malignancies due
to the carcinogenic effects of radiotherapy and
cytotoxic chemotherapy. Another very important aspect of
chemoimmunotherapy, in general is that it may be used on
debilitated patients such as those with AIDS and the
elderly who might otherwise be denied potentially
helpful adjuvant cytotoxic chemotherapy. Further
determination of the mechanisms of these anti-cancer,
immunostimulating and biological response modifying
effects of PSK as well as of other protein-bound
polysaccharides is certainly warranted. Indeed, with
modern cellular and molecular biology techniques, a
better understanding of the specific molecular effects
of PSK on tumor cells as well as leukocytes may be
determined. Much of the research that has been done on
PSK is outlined in this paper and may serve as a
foundation toward determining the mechanisms of action
of this and other protein-bound polysaccharides in the
treatment of cancer. This information may open new doors
in the development of novel strategies for the treatment
of malignancies using adjuvant immunotherapy in
combination with surgery, chemotherapy and/or
radiotherapy.
Publication Types:
PMID: 12168863 [PubMed - indexed for MEDLINE]
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Evaluation of polysaccharopeptide effects against C6
glioma in combination with radiation.
Mao XW,
Green LM,
Gridley DS.
Department of Radiation Medicine (Radiobiology Program),
Loma Linda University and Medical Center, Loma Linda,
Calif. 92354, USA. xmao@dominion.llumc.edu
Long-term control of high-grade brain tumors is rarely
achieved with current therapeutic regimens. The major
goal of this study was to determine whether
polysaccharopeptide (PSP), a crude polysaccharide
peptide extract derived from Coriolus versicolor, a
fungus, could enhance the effects of radiation against
glioma cells in culture and in xenografted tumors in
vivo. PSP significantly augmented radiation-induced
damage to C6 rat glioma cells in vitro. Nude mice
injected subcutaneously with the C6 cells were treated
with PSP (injected intraperitoneally at 2 mg/injection)
and radiation (2 Gy/fraction, 8 Gy in total) using three
different time-dose protocols. Tumor volumes were
consistently smaller in all treated groups compared to
the non-treated tumor-bearing controls except in one
group which received PSP prior to tumor implantation.
The administration of radiation alone resulted in the
slowest tumor progression, whereas PSP alone had no
effect. Furthermore, PSP in combination with radiation
treatment did not increase radiation efficacy. Natural
killer cell, lymphocyte and granulocyte counts in blood
and spleen were significantly higher in PSP-treated
animals, demonstrating that PSP has protective effects
on immunological function. Collectively, these results
warrant further investigation to determine if PSP can be
effectively utilized to upregulate immune responsiveness
in case of neoplasia and other diseases in which
immunosuppression is a prominent feature. Copyright 2001
S. Karger AG, Basel
Publication Types:
PMID: 11574781 [PubMed - indexed for MEDLINE]
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Cell growth and gene modulatory activities of Yunzhi
(Windsor Wunxi) from mushroom Trametes versicolor in
androgen-dependent and androgen-insensitive human
prostate cancer cells.
Hsieh TC,
Wu JM.
Department of Biochemistry and Molecular Biology, New
York Medical College, Valhalla, NY 10595, USA.
The incidence of prostate cancer varies greatly
throughout the world; it is highest in African-Americans
and lowest in the Asian populations of China, India, and
Japan. Geographical differences in both prevalence of
latent prostate cancer and mortality have been
postulated to be influenced by diverse tumor-promoting
and protective factors, both environmental and dietary.
Prostate cancer is a tumor with an extremely long
latency; the pattern of prostate tumorigenesis, in terms
of the display and sequence of appearance of particular
molecular or biochemical features, or morphological
changes, characterizing different stages of the
carcinogenic process, is expected to be heterogeneous.
Some insights into tumor heterogeneity and progression
can be obtained from studies using cell lines,
particularly those derived from different anatomical
sites. The present study aims to investigate whether
hormone-responsive LNCaP and androgen-refractory JCA-1,
PC-3, and DU-145 prostate cancer cells are responsive to
Yunzhi (YZ), a proprietary dietary supplement prepared
from extracts of Trametes versicolor, also known as
Coriolus versicolor (a mushroom consumed by Chinese for
its purported health benefits), and to elucidate its
mechanism of action. Ethanolic extracts (70%) of YZ
significantly reduced LNCaP cell growth, down-regulated
the levels of secreted PSA, but had less effects on the
expression of intracellular PSA and did not affect
levels of the androgen receptor. In
androgen-unresponsive prostate cancer cells, YZ had a
much less pronounced suppressive effect on proliferation
of PC-3 and DU-145 cells, compared to LNCaP, and was
inactive against JCA-1 cells. Western blot analyses show
that the expression of Rb, a key regulatory protein in
G1/S transition, and PCNA, integrally involved in
mammalian cell DNA replication, were significantly
reduced by treatment with YZ in PC-3 and DU-145 cells,
respectively. In contradiction, none of these
biochemical parameters were affected in JCA-1 cells
under identical treatment conditions. Further analysis
shows that YZ increased the levels of signal transducer
and activator family of transcription factors STAT 1 and
STAT 3 in JCA-1 and not LNCaP cells. The greater
sensitivity of LNCaP cells to this polysaccharopeptide
raises the possibility that YZ may be considered as an
adjuvant therapy in the treatment of hormone responsive
prostate cancer; additionally, it may have
chemopreventive potential to restrict prostate
tumorigenic progression from the hormone-dependent to
the hormone-refractory state.
Publication Types:
PMID: 11115542 [PubMed - indexed for MEDLINE]
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Susceptibility of natural killer (NK) cells to
reactive oxygen species (ROS) and their restoration by
the mimics of superoxide dismutase (SOD).
Nakamura K,
Matsunaga K.
Department of Biochemistry, Kitasato University School
of Medicine, Kanagawa, Japan.
Natural killer (NK) cells are susceptible to reactive
oxygen species (ROS), and lose the activity by the
effects of ROS. Cancer bearing hosts usually suffer from
oxidative stress (OS), and the NK-activity decreases to
a significantly lower level than normal controls.
Superoxide dismutase (SOD)-mimicking substances, such as
protein-bound polysaccharide of Coriolus versicolor (Fr)
QUEL (PSK) and iron-chelating chlorine e6-Na (FeCNa),
can restore the NK-activity of cancer bearing hosts,
when collaborating with catalase. Incorporation of
3H-thymidine by ROS-treated NK-cells is not affected,
indicating that these cells are still active in the
nucleic acid metabolism. Intraperitoneal administration
of anti-Asialo GM1 antibody extinguished the NK-activity.
NK-cells affected by ROS lost the adherence to target
cancer cells in both in vitro and in vivo. ROS may
change the surface charge of NK-cells to anionic,
resulting in an inability of adhesion to target cancer
cells which usually show the negative surface charge.
Publication Types:
PMID: 10850363 [PubMed - indexed for MEDLINE]
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Immunomodulation and anti-cancer activity of
polysaccharide-protein complexes.
Ooi VE,
Liu F.
Department of Biology, The Chinese University of Hong
Kong, Shatin, N.T., Hong Kong.
In the last three decades, numerous polysaccharides and
polysaccharide-protein complexes have been isolated from
mushrooms and used as a source of therapeutic agents.
The most promising biopharmacological activities of
these biopolymers are their immunomodulation and
anti-cancer effects. They are mainly present as glucans
with different types of glycosidic linkages such as
(1-->3), (1-->6)-beta-glucans and (1-->3)-alpha-glucans,
and as true herteroglycans, while others mostly bind to
protein residues as polysaccharide-protein complexes.
Three antitumor mushroom polysaccharides, i.e. lentinan,
schizophyllan and protein-bound polysaccharide (PSK,
Krestin), isolated respectively, from Lentinus edodes,
Schizophyllum commune and Coriolus versicolor, have
become large market items in Japan. Lentinan and
schizophyllan are pure beta-glucans, whereas PSK is a
protein-bound beta-glucan. A polysaccharide peptide (PSP),
isolated from a strain of Coriolus versicolor in China,
has also been widely used as an anti-cancer and
immunomodulatory agent. Although the mechansim of their
antitumor action is still not completely clear, these
polysaccharides and polysaccharide-protein complexes are
suggested to enhance cell-mediated immune responses in
vivo and in vitro and act as biological response
modifiers. Potentiation of the host defense system may
result in the activation of many kinds of immune cells
that are vitally important for the maintenance of
homeostasis. Polysaccharides or polysaccharide-protein
complexes are considered as multi-cytokine inducers that
are able to induce gene expression of vaious
immunomodulatory cytokines and cytokine receptors. Some
interesting studies focus on investigation of the
relationship between their structure and antitumor
activity, elucidation of their antitumor mechanism at
the molecular level, and improvement of their various
biological activities by chemical modifications.
Publication Types:
PMID: 10702635 [PubMed - indexed for MEDLINE]
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The use of mushroom glucans and proteoglycans in
cancer treatment.
Kidd PM.
Immunoceuticals can be considered as substances having
immunotherapeutic efficacy when taken orally. More than
50 mushroom species have yielded potential
immunoceuticals that exhibit anticancer activity in
vitro or in animal models and of these, six have been
investigated in human cancers. All are non-toxic and
very well tolerated. Lentinan and schizophyllan have
little oral activity. Active Hexose Correlated Compound
(AHCC) is poorly defined but has shown early clinical
promise. Maitake D-Fraction has limited proof of
clinical efficacy to date, but controlled research is
underway. Two proteoglycans from Coriolus versicolor -
PSK (Polysaccharide-K) and PSP (Polysaccharide-Peptide -
have demonstrated the most promise. In Japanese trials
since 1970, PSK significantly extended survival at five
years or beyond in cancers of the stomach, colon-rectum,
esophagus, nasopharynx, and lung (non-small cell types),
and in a HLA B40-positive breast cancer subset. PSP was
subjected to Phase II and Phase III trials in China. In
double-blind trials, PSP significantly extended
five-year survival in esophageal cancer. PSP
significantly improved quality of life, provided
substantial pain relief, and enhanced immune status in
70-97 percent of patients with cancers of the stomach,
esophagus, lung, ovary, and cervix. PSK and PSP boosted
immune cell production, ameliorated chemotherapy
symptoms, and enhanced tumor infiltration by dendritic
and cytotoxic T-cells. Their extremely high
tolerability, proven benefits to survival and quality of
life, and compatibility with chemotherapy and radiation
therapy makes them well suited for cancer management
regimens.
Publication Types:
PMID: 10696116 [PubMed - indexed for MEDLINE]
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In vitro chemopreventive effects of plant
polysaccharides (Aloe barbadensis miller, Lentinus
edodes, Ganoderma lucidum and Coriolus versicolor).
Kim HS,
Kacew S,
Lee BM.
Division of Toxicology, College of Pharmacy,
Sungkyunkwan University, Changan-ku, Chunchun-dong,
Kyunggi-do, Suwon 440-746, Korea.
A plant polysaccharide, Aloe gel extract, was reported
to have an inhibitory effect on benzo[a]pyrene (B[a]P)-DNA
adduct formation in vitro and in vivo. Hence,
chemopreventive effects of plant polysaccharides [Aloe
barbadensis Miller (APS), Lentinus edodes (LPS),
Ganoderma lucidum (GPS) and Coriolus versicolor (CPS)]
were compared using in vitro short-term screening
methods associated with both initiation and promotion
processes in carcinogenesis. In B[a]P-DNA adduct
formation, APS (180 micrograms/ml) was the most
effective in inhibition of B[a]P binding to DNA in mouse
liver cells. Oxidative DNA damage (by
8-hydroxydeoxyguanosine) was significantly decreased by
APS (180 micrograms/ml) and CPS (180 micrograms/ml). In
induction of glutathione S-transferase activity, GPS was
found to be the most effective among plant
polysaccharides. In screening anti-tumor promoting
effects, APS (180 micrograms/ml) significantly inhibited
phorbol myristic acetate (PMA)-induced ornithine
decarboxylase activity in Balb/3T3 cells. In addition,
APS significantly inhibited PMA-induced tyrosine kinase
activity in human leukemic cells. APS and CPS
significantly inhibited superoxide anion formation.
These results suggest that some plant polysaccharides
produced both anti-genotoxic and anti-tumor promoting
activities in in vitro models and, therefore, might be
considered as potential agents for cancer
chemoprevention.
PMID: 10426820 [PubMed - indexed for MEDLINE]
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A review of research on the protein-bound
polysaccharide (polysaccharopeptide, PSP) from the
mushroom Coriolus versicolor (Basidiomycetes:
Polyporaceae).
Ng TB.
Department of Biochemistry, Faculty of Medicine, Chinese
University of Hong Kong, Shatin, N.T., Hong Kong.
1. Protein-bound polysaccharides, designated as PSK and
PSP, have been isolated from the CM-101 strain and the
COV-1 strain, respectively, of the mushroom Coriolus
versicolor. This article aims at summarizing existing
research findings about PSP since information on PSK is
well documented. 2. PSP possesses a molecular weight of
approximately 100 kDa. Glutamic and aspartic acids are
abundant in its polypeptide component, whereas its
polysaccharide component is made up of monosaccharides
with alpha-1,4 and beta-1,3 glucosidic linkages. The
presence of fucose in PSK and rhamnose and arabinose in
PSP distinguishes the two protein-bound polysaccharides,
which are otherwise chemically similar. 3. PSP is
classified as a biological response modifier. It
induces, in experimental animals, increased
gamma-interferon production, interleukin-2 production,
and T-cell proliferation. It also counteracts the
depressive effect of cyclophosphamide on white blood
cell count, interleukin-2 production and delayed-type
hypersensitivity reaction. Its antiproliferative
activity against tumor cell lines and in vivo antitumor
activity have been demonstrated. A small peptide with a
molecular weight of 16-18 kDa originating from PSP has
been produced with antiproliferative and antitumor
activities. 4. PSP administered to patients with
esophageal cancer, gastric cancer and lung cancer, and
who are undergoing radiotherapy or chemotherapy, helps
alleviate symptoms and prevents the decline in immune
status.
Publication Types:
PMID: 9457474 [PubMed - indexed for MEDLINE]
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Effects of OK-432 (picibanil) on the estrogen
receptors of MCF-7 cells and potentiation of
antiproliferative effects of tamoxifen in combination
with OK-432.
Aoyagi H,
Iino Y,
Takeo T,
Horii Y,
Morishita Y,
Horiuchi R.
Second Department of Surgery, Gunma University School of
Medicine, Maebashi, Japan.
OK-432 (picibanil), a streptococcal preparation, has a
strong biological response modifier (BRM) function and
is expected to produce clinical improvement and
prolongation of survival in treated cancer patients in
Japan. We were interested in whether OK-432 augments
estrogen receptor (ER) levels in breast cancer. To
investigate the effect of the BRMs on cellular growth
and the characteristics of ER and progesterone receptors
(PgR) in the human breast cancer cell line MCF-7, we
used OK-432, Krestin (PSK), a protein-bound
polysaccharide extracted from Coriolus versicolor, and
lentinan, a fungal branched (1...3)-beta-D-glycan. OK432
and PSK dose dependently inhibited DNA synthesis of
MCF-7 cells, and the 50% inhibitory concentrations of
OK-432 and PSK were 1.2 KE (klinische Einheit, clinical
unit)/ml and 200 micrograms/ml, respectively. Lentinan
showed no direct anticancer effect in vitro. We found
that OK-432 induced a 2-fold increase in ER levels in
MCF-7 cells at 0.005 KE/ml, but not in PgR. Lentinan and
low-dose PSK did not change ER or PgR levels, but
high-dose PSK decreased ER and PgR. We also studied the
combined effect of OK-432 and antiestrogens, tamoxifen
(TAM) and DP-TAT-59. The combined treatment with OK-432
and TAM showed an additive inhibitory effect on MCF-7
cells. These results suggest that OK-432 may augment the
therapeutic effect of TAM in breast cancer.
Publication Types:
PMID: 9260604 [PubMed - indexed for MEDLINE]
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Dose intensity of uracil and tegafur in postoperative
chemotherapy for patients with poorly differentiated
gastric cancer.
Sugimachi K,
Maehara Y,
Ogawa M,
Kakegawa T,
Tomita M.
Department of Surgery II, Faculty of Medicine, Kyushu
University, Fukuoka, Japan.
A retrospective analysis of postoperative chemotherapy
had shown the continuous administration of UFT, an oral
preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur)
and uracil at a molar ratio of 1:4, to be effective for
poorly differentiated gastric cancer. We therefore
sought to determine prospectively the effective dose of
postoperative chemotherapy with UFT for patients with
poorly differentiated gastric cancer following a
curative resection. We determined the effect of the
combined intravenous administration of mitomycin C (MMC)
and oral treatment with protein-bound polysaccharide
Kreha (PSK), extracted from the basidiomycete Coriolus
versicolor, and UFT at a dose of either 8 mg/kg or 12
mg/kg daily for 1 year. A total of 224 patients with
poorly differentiated stage II-IV gastric cancer were
entered into this study after undergoing a curative
resection. No differences were observed between the two
treatment groups in terms of prognostic factors, the
toxicity rate or the doses of the drugs prescribed,
other than UFT. The higher dose of UFT in maintenance
therapy led to a decrease in the recurrence rate (P <
0.05), and increases in disease-free survival and
cause-specific survival (P < 0.05). UFT at 12 mg/kg in
postoperative chemotherapy was thus found- to improve
the postoperative results with no increase in toxicity
for poorly differentiated gastric cancer, and is also
cost-effective for outpatients.
Publication Types:
PMID: 9219507 [PubMed - indexed for MEDLINE]
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Polysaccharide peptide (PSP) restores
immunosuppression induced by cyclophosphamide in rats.
Qian ZM,
Xu MF,
Tang PL.
Department of Applied Biology and Chemical Technology,
Hong Kong Polytechnic University, Hung Hom, Kowloon,
Hong Kong.
Polysaccharide peptide (PSP) is a protein-bound
polysaccharide extracted from an edible mushroom,
Coriolus versicolor. Effects of PSP (2g/kg/day) on
cyclophosphamide (CPA, 40 mg/kg/2 days)-induced
immunosuppression were investigated by determining
lymphocyte proliferation, Natural killer (NK) cell
formation, IgG and IL-2 concentration, WBC count and the
weight of organs after rats were treated with or without
CPA in the presence or absence of PSP. The results
demonstrated that PSP possessed immunopotentiating
effect, being effective in restoring CPA-induced
immunosuppression such as depressed lymphocyte
proliferation, Natural Killer cell function, production
on white blood cell and the growth of spleen and thymus
in rats as well as in increasing both IgG and IL-2
production on which CPA did not have significant effects
under the conditions of our experiments. PSP can partly
restore CPA-induced immunosuppression. Based on our
findings and the data accumulated so far, it was
suggested that PSP should be considered as an useful
adjuvant especially combined with CPA or other
chemotherapy in clinical treatment of cancer patients.
The mechanism by which PSP restores the
immunosuppression induced by CPA is unclear.
Publication Types:
PMID: 9166995 [PubMed - indexed for MEDLINE]
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Immunotherapy with low-dose interleukin-2 and a
polysaccharopeptide derived from Coriolus versicolor.
Mao XW,
Archambeau JO,
Gridley DS.
Department of Radiation Medicine, Loma Linda
University/Independent Order of Foresters Cancer
Research Laboratory, CA 92350, USA.
The purpose of the present study was to evaluate the
therapeutic efficacy of locally administered low-dose
interleukin-2 (IL-2) and a polysaccharopeptide (PSP)
derived from Cariolous versicolor in a herpes virus Type
2-transformed murine tumor (H238) model and to determine
possible mechanisms of action. BALB/c mice were
inoculated subcutaneously (s.c.) with H238 tumor cells
and randomized into groups: a) no tumor and no treatment
control, b) tumor and no treatment control, c) tumor +
IL-2 at 0 to 4 days, d) tumor + PSP at 0 to 10 days, e)
tumor + IL-2 at 0 to 4 days + PSP at 0 to 10 days, and
f) tumor + IL-2 at 15 to 19 days + PSP at 15 to 25 days.
The IL-2 was administered s.c. at 2 x 10(4) i.u./mouse/injection;
PSP was given s.c. at 2 mg/mouse/injection. No obvious
toxicity was noted during the treatments. IL-2 and, to a
lesser extent, PSP significantly slowed (p < 0.05) tumor
progression when given alone immediately after tumor
cell injection. The combination of the two modalities
did not significantly enhance the antitumor effect of
IL-2 alone. However, mice receiving both agents had IL-2
in the plasma, their tumors expressed low levels of
transforming growth factor-beta, and their splenocyte
response to mitogenic stimulation was significantly
higher than in untreated controls. Changes in blood
leukocyte populations and splenic oxidative burst
capacity were associated with tumor presence, but not
with the type of treatment. In vitro assays showed that
both IL-2 and PSP can suppress the uptake of
3H-thymidine by tumor cells and that the effect is more
pronounced whent the agents are used in combination.
These results indicate that IL-2 and PSP can slow
progression of H238 tumors and that the mechanisms of
action may be related to their direct cytotoxic effects,
as well to their immunomodulatory properties.
Publication Types:
PMID: 10851500 [PubMed - indexed for MEDLINE]
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Antitumor effects of a refined polysaccharide peptide
fraction isolated from Coriolus versicolor: in vitro and
in vivo studies.
Dong Y,
Kwan CY,
Chen ZN,
Yang MM.
Department of Physiology, Faculty of Medicine,
University of Hong Kong, Pokfulam, Hong Kong.
RPSP, a refined polysaccharide peptide fraction isolated
by fast performance liquid chromatography (FPLC) from
the crude powder of total peptide-bound polysaccharides
of cultivated Coriolus versicolor Cov-1 dose-dependently
inhibited the proliferation of a human hepatoma cell
line (HEPG2). The effective dose causing 50% inhibition
following 3-day exposure to RPSP was 243 +/- 36
micrograms/ml for HEPG2. However, little or no
inhibitory effects were detected in normal human foetal
hepatocytes. On the other hand, in the pretreatment
group, in which RPSP was administered i.p. for two weeks
before sarcoma 180 inoculation in nude mice, the
incidence of tumor growth was less (2 out of 5 mice)
than that of the control group (all 5 mice). The tumor
size of the control group was about 3-5 times bigger
than that of the pretreatment group. In tumor-bearing
nude mice, 5 days after sarcoma 180 inoculation, i.v.
administration of RPSP significantly suppressed the
growth of tumor mass. The inhibition rate was 93.6% on
day 13. Furthermore, administration of RPSP did not
cause any pathological lesions in vital organs of
rabbits such as heart, liver, spleen, lung and kidney.
In conclusion, these results indicate that RPSP acts by
directly suppressing tumor cell growth in vitro and the
prevention of in vivo growth of tumor mass is probably
mediated also via its immunomodulating effects.
Publication Types:
PMID: 8774067 [PubMed - indexed for MEDLINE]
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Effects of Coriolus versicolor polysaccharides on
superoxide dismutase activities in mice.
Wei WS,
Tan JQ,
Guo F,
Ghen HS,
Zhou ZY,
Zhang ZH,
Gui L.
Department of Pharmacology, Second Military Medical
University, Shanghai, China.
AIM: To study if Coriolus versicolor polysaccharides (CVP)
influence the superoxide dismutase (SOD) activities in
mice. METHODS: Normal, tumor-bearing, and radiated ICR
mice were injected ip with CVP daily for 3-15 d. The SOD
activity was assayed by epinephrine autoxidation test.
RESULTS: The SOD activities in lymphocytes and thymus
were increased by CVP in both the normal mice with or
without delayed hypersensitivity (DH). In tumor-bearing
mice, CVP exerted not only inhibitory effects on tumor,
growth and SOD activity in tumor tissue but also
complete or partial restorative effects on the
suppressed DH and on the declined SOD activities in
lymphocytes, spleen, and thymus. The total SOD and
manganese-containing SOD (MnSOD) activities in
lymphocytes and thymus were dose-dependently enhanced by
CVP (5-20 mg.kg-1) on d 3 after the tumor
transplantation. In the mice exposed to 60Co (3 or 6 Gy),
DH and SOD activities were dose-dependently decreased.
These changes were completely or partly prevented by CVP.
CONCLUSION: CVP exerted the favorable effects on SOD
activities in mice. Coriolus versicolor polysaccharides
(CVP) exert inhibitory effects on experimental and
clinical tumors. These effects are presumed to be
mediated mainly by host-defence mechanism, especially
immunological responeses. Superoxide dismutase (SOD)
plays an important role in protecting cells against
superoxide radical (O2-.) damages and over-production of
O2-. or SOD abnormities exist in many diseases. The
present study was to investigate if the CVP could exert
some favorable effects on SOD activities in vivo.
PMID: 9772673 [PubMed - indexed for MEDLINE]
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