Category Archives: Medical Studies

Clinical Trials, Lymphocytes, Medical Studies, PSP

The Physio-Chemical Characteristics of the Polysaccharide-peptide (PSP) of Coriolus versicolor (Yun Zhi)

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Q.Y. Yang, S.C. Yong and X.T. Yang

Shanghai Normal University

Abstract

PSP is an anticarcinogen and immunological regulator identified as a polysaccharide peptide which has been extracted from the deep layer cultivated mycelia of Coriolus versicolor. Infrared spectrophotometer at wavelenghts of 3432 cm-1, 1621 cm-1 and 1073 cm-1 produces three absorption bands.

The N.M.R. of PSP has the characteristic to show absorption at 1.0-2.5 ppm, 3.0-3.4, 4.5, 5.4 ppm and broad absorption in the region of 3.0-4.3 ppm.

Use spectrophotometer to determine the effluent separated from the column of gel chromatography (Sephadex G-75), The results shown that maximum absorption peaks of polypeptide and polysaccharides are found in the homeo-collecting tubes.

The polysaccharide portion is composed of the five monsaccharides, galactose, glucose, mannose, xylose, and fucose. The amino acids most frequently found in the polypeptide are aspartic and glutamic. PSP has no sharply defined fusion point. It is insoluble in methyl alcohol, pryridine, benzene, hexane, and chloroform but is very soluble in hot water. The pH value of its 1% water solution is 6.6. It is heat and light stable. &nbp; When kept at a temperature of 100oC for 48 hours or irradiated with ultraviolet light for 30 hours there is essentially no change in composition. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) the molecular weight has been calculated at about 1×105 Dalton.

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Cancer, Medical Studies, PSP

The cell death process of the anticancer agent polysaccharidepeptide (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.

Abstract

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.

PMID: 15870943 [PubMed – indexed for MEDLINE]

PubMed

U.S. National Library of Medicine

National Institutes of Health

Publication Types, MeSH Terms, Substances

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Cancer, in vitro, Medical Studies, PSK, Tumor

Suppression of cancer cell growth in vitro by the protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) with SOD mimicking activity.

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Cancer Biother. 1994 Spring;9(1):63-9.

Kobayashi Y, Kariya K, Saigenji K, Nakamura K.

Molecular Biology Laboratory, Kotasato University School of Medicine, Kanagawa, Japan.

Abstract

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the mimicking activity of superoxide

dismutase (SOD). Examination was made of the suppressive effects of PS-K on cancer cell lines cultured in vitro. The

SOD activity of LLC-WRC-256 (Walker 256 fibrosarcoma) cell lines was less than that of NRK-49F (rat normal kidney

fibroblast), H4-II-E (rat hepatoma) and H4-II-E-C3 (rat hepatoma) cell lines. This activity in Walker 256 fibrosarcoma cells

increased by 3.6 times and H2O2 concentration, by 2.56 times by PS-K 500 micrograms/ml. Cell proliferation was

consequently suppressed and living cells decreased to less than 50% of the cells cultured without PS-K. Catalase and

glutathione peroxidase activity changed little by PS-K. The sensitivity of cancer cells to PS-K can be predetermined based

on SOD activity in tumor tissue.

PMID: 7812358 [PubMed – indexed for MEDLINE]

PubMed

U.S. National Library of Medicine

National Institutes of Health

MeSH Terms, Substances

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Cancer, Chemotherapy, Medical Studies, PSK, Tumor

Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. 5-Year results from the Nishi-Nippon Group of the Adjuvant Chemoendocrine Therapy for Breast Cancer Organization.

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Cancer. 1992 Nov 15;70(10):2475-83.

Toi M, Hattori T, Akagi M, Inokuchi K, Orita K, Sugimachi K, Dohi K, Nomura Y, Monden Y, Hamada Y, et al.

Department of Surgery, Hiroshima University, Japan.

Abstract

BACKGROUND: A randomized adjuvant trial was conducted from October 1982 to January 1985 to evaluate the addition

of tamoxifen (TAM) to combination chemotherapy with perioperative mitomycin C (MMC) and ftorafur (FT) for patients with

estrogen receptor (ER)-positive tumors and the addition of PSK, a biologic response modifier, to MMC+FT chemotherapy

for patients with ER-negative tumors in operable Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral TAM

daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2 years. Intravenous MMC (13 mg/m2) was given on the day

of operation.

METHODS: A total of 967 patients were entered and randomized by stratification based on ER status and

staging (1978 International Union Against Cancer [UICC] criteria at the time of trial execution). Of 967 patients, 914

(94.5%) were evaluable. At 5-year follow-up, significant prolonged overall survival (OS) and relapse-free survival (RFS)

times were seen with the addition of TAM in patients with ER-positive and Stage IIIA T3N0 cancer (1987 UICC-American

Joint Committee on Cancer [AJCC] criteria); however, no significant survival benefit from TAM was seen in patients with

ER-positive and Stage IIA T2N1 cancer. There was no significant difference between regimens, with or without PSK, in

patients with ER-negative disease.

RESULTS: Results of subset analyses suggested a benefit from TAM in

postmenopausal patients with ER-positive and Stage IIA T2N1 cancer and a benefit from PSK in patients with

node-negative, ER-negative, and Stage IIA T2N1 cancer.

CONCLUSIONS: The 5-year results of the current trial showed a

survival advantage by the addition of TAM to chemotherapy in patients with ER-positive and Stage IIIA T3N0 cancer.

PMID: 1423177 [PubMed – indexed for MEDLINE]

PubMed

U.S. National Library of Medicine

National Institutes of Health

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Medical Studies, PSP

The Influence of PSP on the Behavior and Growth of the Fetus in Rats

Zheng-de Zhang1, Zhen-bin Qian2, Lan-feng Zhou2 and Bin Xu1 1 Shanghai Institute of Materia Medica, Academia Sinica 2 Department of Toxicology, Shanghai Institute of Labour Health and Occupational Diseases

Abstract

PSP is a new immunomodulating agent prepared and developed by Professor Qing-yao Yang. In the present work its influence on the behavior and growth of fetus in 1st and 2nd generation of rats was investigated.

For behavior study the squirrel wheel test, rotating cylinder test and passive avoidance test were performed, PSP was administered orally at 60, 600 and 6000mg/kg. The results showed that no marked difference in the change of behavior was found between the control and treatment groups. The brain weights of two-generation rats had no marked change either.

For teratogeny test 110 rats were involved PSP was administered orally at 60, 600 and 6000mg/kg in different groups for 10 days. The conditions of the maternal body, embryonic survival and the function and growth of the fetuses were examined. After statistical tests no marked difference was observed in the control and treatment groups.

The data observed showed that PSP has no noticeable toxicity on fetus growth and on the behavioral performance of 1st and 2nd generation rats.

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in vitro, Medical Studies, PSK, PSP

PSP and PSK

Informatioin Office of the Research Institute of Fungi Shanghai Teachers University

PSP and PSK are the 2 products of Yun Zhi ratified by Chinese Ministry of Public Health and Japanese Ministry of Public Health respectively.

PSK was first manufactured by Kureha Chemical Industry Co. Ltd. The PS in PSK represents polysaccharide and K represents the first alphabet of the name of this Company. It was originally written as PS-K and was later changed to PSK. o; The commercial name of the product is Krestin.

PSP was prepared by Professor Qing-yao Yang. It is like PSK and is also a kind of compound polysaccharide. On the molecules of the polysaccharide, the small molecular protein (polypeptide) is connected. So it is called Yun Zhi Duo Tang Tai or Yun Zhi Tang Tai. The Tang Tai English names were originally glycopeptide, proteoglucan, glycosaminoglucan, etc. But the polysaccharide is all composed of N-acetyl-amino-hexose. But the polysaccharides of PSP and PSK are not composed of N-acetylamino-hexose. So it is not suitable to use the name. So the word “polysaccharopeptide” or “polysaccharide-peptide” is used and is abbreviated as PSP or Ps-p.

According to the different degrees of extraction, there are a series of PSP products. PSP directly extracted from the mycelia of Yun Zhi is called Yun Zhi Polysaccharide-peptide (Trade mark Qing Kang) and PSP polysacchardie-peptide (Landford). The former is sold on the market of Mainland China and the latter is according to the export specifications and is sold overseas. These 2 products are mainly used for tumorous patients.

The essence of the product is obtained by further isolation of the crude product. It is called Essence of Mushroom (Yun Zhi) (The sole distributor is Winsor Health Products Ltd., Hong Kong) used for healthy purposes.

Japan is quite specialized in the research of Yun Zhi. Besides PSK, Hirose, S. et al, (1970), Naruse S. and Takeda S. (in 1970) and Sugiura M. (in 1980) isolated two anticancerous components of the mycelia of Yun Zhi respectively. The former is called

ASTO and latter D–II. In addition, Ito H. et al (in 1974) extracted from the fermented mash of Yun Zhi an anti-tumor component which does not contain protein and it is called Coriolan. Its chemical components are glucans (by Hayashida S. et al, in 1992). But the above-mentioned three components still remain in the process of pharmacological research and was not used in clinical application.

Though PSP and PSK are all a kind of protein bound polysaccharide and are all extracted from the deep layer cultivated mycelia, yet they use the different strains, fermented medium and different extracted methods. Thus there is a certain difference between PSP and PSK. It is known that in the polysaccharide of PSP there is fucose, while there is no fucose in PSP, which contains arabinose and rhamnose; while there are no such ingredients in PSK. On the other hand, according to the pharmacological and clinical research, PSP has the definite effect of alleviating pain and increasing appetite, while there is no such report on PSK. Comparison of Two Characterisitics of PSP and PSK

Items compared

Similarities

Dissimilarities

Fungi

Yun Zhi Coriolus versicolor (Fr.) Quel

PSP: Cov-1 strain PSK: CM-101 strain

Drug produced

PSP: capsule PSK: loose package

Powder color

brown

PSP: brown PSK: dark brown

Raw materials

deep-layer cultivated mycelia (2N)

Fermentation technology

with glucose as the main carbon source (25oC, 3 days)

PSP: nitrogenous source: soya beancake powder PSK: nitrogenous source: peptone and yeast cake

Extract and isolate

obtained by immersion in hot water

PSP: isolate by alcoholic precipitation PSK: isolate by salting out with (NH4)2SO4

Medicinal ingredients

protein bound polysaccharide; average molecular wt. 1 x 105 Da the polysaccharide is formed from many monosaccahrides containing

PSP: polysaccharides contain arabinose and rhmanose, but no fucose PSK: polysaccharides do not

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Cancer, in vitro, Medical Studies, Tumor

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

Liang-zhong Xu, Jun Han and Gang Chen Laboratory of Pathology, Cancer Institute, Shanghai Medical University

Abstract

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.

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Immunotherapy, in vitro, Medical Studies, PSP

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

Jin-Xu Zhou, Xin-li Shen, Zu-ming Shen, Xiao-yu Li Department of Pharmacology I Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai 200031

Abstract

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

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Chemotherapy, Medical Studies, PSP

Clinical Experience in the Use of PSP

W.C. Xue and T.F. Liu Cancer Hospital, Shanghai Medical University

There is no really effective treatment for moderate and advanced stages of esophageal carcinoma. Although surgery for the earlier cases has been able to give a 5 years survival rate of 28.7%, such operable cases are relatively few. By far the greater majority are already in stage III to IV when first seen in the clinic, and radiotherapy alone in these cases has given a 5 years survival rate of only 8-14%. In order to improve treatment results, a variety of chemotherapeutic agents have been used in combination surgery, but so far no really effective drug has been found.

The drug PSP (polysaccharide-peptide of Coriolus versicolor) has been discovered and produced by Professor Qing-yao Yang of. It is a new anti-cancer and immuno-regulatory drug, similar to PSK (Krestin) but the effective component has been found to be larger than PSK. Experimental data has proved these properties of PSP, and in vitro as well as in vivo studies have all proved that PSP is superior to PSK. Of course, as is the case with all new drugs, the ultimate proof of its value will have to be shown by clinical application.


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Cancer, Medical Studies, Prostate Cancer

Cell growth and gene modulatory activities of Yunzhi (Windsor Wunxi) from mushroom Trametes versicolor in androgen-dependent and androgen-insensitive human prostate cancer cells. TC Hsieh, JM Wu. Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA. The incidence

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.

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