Antitumor Effect of Polysaccharide Peptide of Coriolus versicolor (PSP) and its Mechanism

Jin-Xu Zhou, Xin-li Shen, Zu-ming Shen, Xiao-yu Li

Polysaccharide peptide of Coriolus versicolor (PSP) is a new anti-tumor and immunomodulating drug. In this paper PSP showed direct inhibition on the cell proliferation of sarcoma 180 in vitro and inhibitory effect on the growth of murine sarcoma 180 in vivo. Owing to its direct cytotoxic effect was not strong, but at lower concentrations (10-20ug/ml) of PSP promoted the proliferation of T and pre-T cells of mouse thymus, increased the thymus weight, provided more number of lymphocytes, prevented the involuation of thymus in tumor bearing mice and antagonized the anti-tumor action of PSP combined with antilymphocyte serum. It is suggested the principal mechanism of anti-tumor activity of PSP was T-cell mediated cytotoxicity.
It has been known that some polysaccharides and polysaccharide peptide isolated from various natural sources, especially isolated from Basiodiomycetes have certain anti-tumor activities. The polysaccharide contained a main chain of an alpha and beta (1-4) glucan and a tightly bound 15-38% polypeptides (PSP) isolated from Coriolus versicolor (Fr) Quel. (Cov-1) by Professor Qing-yao Yang also exhibited antitumor action against mouse sarcoma 180 in vitro and in vivo. Recent experiments suggest three possible mechanism by which these PSP might act: (1) Potentiating of T-cell mediated cytotoxicity which killed more number of target-tumor cells. (2) Definite concentration of PSP produced direct cytotoxic activity in vitro. (3) Induction of tumorcidal macrophages killed more cancer cells. In this paper the antitumor action of PSP and its possible mechanism are reported.

Antioxidant properties of several medicinal mushrooms.

JL Mau, HC Lin, CC Chen.

Three species of medicinal mushrooms are commercially available in Taiwan, namely, Ganoderma lucidum (Ling-chih), Ganoderma tsugae (Sung-shan-ling-chih), and Coriolus versicolor (Yun-chih). Methanolic extracts were prepared from these medicinal mushrooms and their antioxidant properties studied. At 0.6 mg/mL, G. lucidum, G. lucidum antler, and G. tsugae showed an excellent antioxidant activity (2.30-6.41% of lipid peroxidation), whereas C. versicolor showed only 58.56%. At 4 mg/mL, reducing powers were in the order G. tsugae (2.38) approximately G. lucidum antler (2.28) > G. lucidum (1.62) > C. versicolor (0.79). At 0.64 mg/mL, scavenging effects on the 1,1-diphenyl-2-picrylhydrazyl radical were 67.6-74.4% for Ganoderma and 24.6% for C. versicolor. The scavenging effect of methanolic extracts from G. lucidum and G. lucidum antler on hydroxyl radical was the highest (51.2 and 52.6%) at 16 mg/mL, respectively. At 2.4 mg/mL, chelating effects on ferrous ion were in the order G. lucidum antler (67.7%) > G. lucidum (55.5%) > G. tsugae (44.8%) > C. versicolor (13.2%). Total phenols were the major naturally occurring antioxidant components found in methanolic extracts from medicinal mushrooms. Overall, G. lucidum and G. tsugae were higher in antioxidant activity, reducing power, scavenging and chelating abilities, and total phenol content.

Antimetastatic Effects of P5K (Krestin), a Protein-bound Polysaccharide Obtained from Basidiomycetes: An Overview

Hiroshi Kobayashi, Kenichi Matsunaga,1 and Yoshiharu Oguchi

P5K, a protein-bound polysaccharide obtained from cultured mycelia of Coriolus versicolor in basidiomycetes, is a biological response modifier, diverse operations of which include an antitumor action. We have previously reviewed recent research which had demonstrated that in animals, P5K has a preventive effect on chemical carcinogen-induced, radiation induced, and spontaneously developed carcinogenesis (Kobayashi et aL, Cancer Epidemiol., Biomarkers & Prey., 2: 271-276, 1993). We now focus on the effects of PSK once the progression of carcinogenesis has begun, and review what is now known of the preventive action of PSK on cancer metastasis.

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Sequential batch culture studies for the decolorisation of reactive dye by Coriolus versicolor.

Sanghi R, Dixit A, Guha S.

Facility for Ecological and Analytical Testing, Indian Institute of Technology-Kanpur, Kanpur 208 016, India. rsanghi@iitk.ac.in

Abstract

The white rot fungus Coriolus versicolor could decolorise reactive dye Remazol Brilliant Violet to almost 90%. The fungal mycelia removed color as well as COD up to 95% and 75%, respectively, in a batch reactor. Decolorising activity was observed during the repeated reuse of the fungus. It was possible to substantially increase the dye decolorising activity of the fungus by carefully selecting the operational conditions such as media composition, age of fungus and nitrogen source. The fungal pellets could be used for eight cycles during the long term operation, where medium and dye was replenished at the end of each cycle and the fungus was recycled. Presence of a nitrogen source and nutrient content of media played an important role in sustaining the decolorisation activity of the fungus. The form of nitrogen source (e.g. peptone vs. urea) was also important to maintain the decolorising activity with peptone showing better decolorisation.

PMID: 15882943 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/15882943

PSP Inventor Dr. Yang Gives inLife Exclusive Distribution Rights for Coriolus versicolor PSP

Irvine, California (September 22, 2010) inLife, LLC, distributors of science-based Health & Wellness products today announced that Professor Q.Y. Yang, inventor of the Coriolus versicolor mushroom Polysaccharopeptide (PSP, also commonly called Polysaccharide-peptide) extract, has given to inLife, LLC the exclusive distribution rights wherever inLife distributes its products. Dr. Yang is recognized as the world’s foremost expert on Coriolus versicolor research. He is currently the director of the Research Institute of Microbiology & Immunology of Shanghai Teachers University, where he invented the technique of submerged cultivation of mycelia of mushrooms.

“inLife is thrilled to have learned today that Dr. Yang has entrusted inLife with the honor of distributing his Coriolus versicolor PSP. There are literally today millions of people who can benefit from Dr. Yang’s PSP and we are very excited that inLife will be the messenger to enlighten so many about its efficacies and properties” stated Craig Youngblood, President and CEO of inLife, LLC.

Dr. Yang is responsible for identifying and isolating the most effective COV-1 strain from over 100 different strains of Coriolus versicolor. In recognition of his invention of PSP and also his outstanding achievements in traditional Chinese medicine, Professor Yang has been recognized with many international honors. Dr. Yang has also received a patent for his discovery of PSP extraction process.

About Coriolus versicolor

The Coriolus versicolor mushroom is one of the most widely studied supplements for its immune building properties. Worldwide, there have been over 400 animal and human studies on Coriolus versicolor with over a dozen placebo-based human trials conducted in the west. Traditionally, the Coriolus versicolor mushroom (known as Yun-zhi or cloud mushroom in China) has been used in China for several thousand years because of its immune boosting capabilities. In the 1980s, Dr. Yang conducted further studies and was able to isolate a much more potent strain using a different, alcohol-based extraction process. The result was Polysaccharopeptide or PSP. In the United States, top-ranked hospital and research institutes have reported that Coriolus versicolor helps boost the body’s immune system with limited side effects and safety of daily oral doses for extended periods of time. In addition, Coriolus versicolor and its potential positive effects has been studied very closely by M.D. Anderson, University of Texas, Loma Linda University, Beth Israel Deaconess Medical Center (a teaching hospital of Harvard Medical School) , The University of San Diego, Sloan-Kettering Center (New York), and Bastyr University (Kenmore, Washington) just to name a few.

inLife Immune Builder with PSP and PSK

inLife offers Coriolus versicolor as a Daily Dietary Supplement in capsule form to help maintain and stimulate the body’s immune system. Coriolus versicolor and its high-potency extracts, PSK and PSP are among the most widely studied supplements for their immune building properties. One would be hard-pressed to find another immune boosting product that has had more research completed or positive comments associated with it. The amount of worldwide comments and studies is compelling. InForce Immune Builder is a proprietary blend of both Polysaccharide-K (PSK) and Polysaccharopeptide (PSP). Both offer much needed immune building assistance and they can be taken on a daily basis. The products are bottled in the United States in an FDA registered bottling facility that is CGMP compliant (Current Good Manufacturing Practices).

About inLife LLC

Founded in 2007, inLife has been very successful in bringing to market products that have efficacies that are soundly based on scientific research. inLife products are now available in the U.S. as well as the U.K, Canada and Spain. For more information on inForce Immune Builder and the company, please review www.myinlife.com. For further details on inForce, journalists may contact Thomas Kiklas directly at 949-648-2525.

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About inLife, LLC Founded in 2007, inLife has been very successful in bringing to market products that have efficacies that are soundly based on scientific research. inLife products are now available in the U.S. as well as the U.K, Canada and Spain. For more information on inForce Immune Builder and the company, please review www.myinlife.com. For further details on inForce, journalists may contact Thomas Kiklas directly at 949-648-2525.

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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.

Abstract

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.

PMID: 15908782 [PubMed – indexed for MEDLINE]Free Article

http://www.ncbi.nlm.nih.gov/pubmed/15908782

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.

Abstract

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.

PMID: 15944782 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/15944782

Antimetastatic effect of PSK, a protein-bound polysaccharide, against the B16-BL6 mouse melanoma.

We examined the effect of PSK, a protein-bound polysaccharide, upon in vivo metastasis and in vitro invasion of the B16-BL6 mouse melanoma cells. (1) PSK suppressed in vivo artificial and spontaneous lung metastases of B16-BL6 in C57BL/6 mice. (2) PSK in a dose-dependent fashion suppressed in vitro invasion and chemotaxis of the tumor cells using filters coated with a reconstituted basement membrane. (3) PSK had little effect on DNA synthesis in tumor cells in vitro, but suppressed tumor cell adhesion to, degradation of, and haptotaxis to components of the basement membrane. (4) PSK suppressed the binding of tumor cells to components of the basement membrane. These findings suggest that PSK may suppress metastasis through inhibition of tumor cell invasion and that this effect is the result of interactions between PSK and components of the basement membrane.

Anticancerous Effect of PSP Purified Products and KS-2 on Human Tumor Cell Lines in Vitro

The anticancer effects of PSP purified products, PSP-A, PSP-B, PSP-C and crude product PSP-Cr and KS-2 were compared on four human tumor cell lines in vitro. It was found that the inhibition rate of cell proliferation of PSP-A was higher than that of PSP-Cr, PSP-B and PSP-C (P<0.05). On SPC cells, the inhibition rate of PSP-A at a dosage of 1000ug/ml was 62.7%, being the highest as compared with those on the other three cell lines.
The effect of the inhibition of KS-2 on Mei tumorous cells is obvious. Its inhibition rate is 62.5%.
Morphological changes were seen in all the four cell lines, especially in SPC cells after PSP-A treatment.

ANALYSIS OF IMMUNOMODULATING CYTOKINE mRNAs IN THE MOUSE INDUCED BY MUSHROOM POLYSACCHARIDES

The immunomodulating action of two mushroom antitumor polysaccharides, polysaccharide-protein complex (PSPC) and lentinan, was elucidated through analysing the expression profile of cytokines during a time course (0 h to 48 h) after their administration. Among the 5 cytokine genes, the induction of a marked increase in the mRNA levels of IL-la, IL-lp, TNF-a, IFN-)I and M-CSF by PSPC and lentinan was observed in the peritoneal exudate cells and splenocytes. However, the time point of their increased production was different after PSPC and lentinan administration.

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