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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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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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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Evaluation of polysaccharopeptide effects against C6 glioma in combination with radiation.

XW Mao, LM Green, DS Gridley.

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.

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Clinical observation on alleviating chemotherapy side effects of psp in treating gastric careinoma

Clinical observation on alleviating chemotherapy side effects of psp in treating gastric carcinoma (in Chinese)

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Effects of Coriolus versicolor polysaccharide B on monocyte chemoattractant protein 1 gene expression in rat.

LC Song, HS Chen, N Lou, C Song, J Zeng, TH Fu.

Laboratory for Molecular Pharmacology, Department of Hygiology, First Military Medical University, Guangzhou 510515, China. songlc@fimmu.edu.cn

AIM: To investigate the effect of Coriolus versicolor polysaccharide B (CVPS-B), a new water-soluble component of polysaccharides from the fungus Coriolus versicolor (Fr) L on monocyte chemoattractant protein-1 (MCP-1) gene expression in rat splenocytes. METHODS: Expression of MCP-1 mRNA in rat splenocytes was examined by reverse transcription-polymerase chain reaction (RT-PCR) with beta- actin as an internal standard. Sequencing of RT-PCR products was performed to confirm their specificity in MCP-1 gene composition. RESULTS: (1) Without pre-treatment of lipopolysaccharide (LPS), the relative MCP-1 mRNA expression ratios (MCP-1/beta-actin) for the saline control group and for CVPS-B groups in 3 different doses (10, 20, and 30 mg . kg-1 . d-1, ip, for 4 d) were 1.4 +/- 0.3, 1.6 +/- 0.4, 1.7 +/- 0.5, and 1.5 +/- 0.4, respectively (P > 0.05); (2) LPS (10 microg . kg-1, ip) enhanced the expression of MPC-1 mRNA by the ratio of 114 %; (3) pre-treatment with CVPS-B of 4 different doses (5, 10, 30, and 50 mg . kg-1 . d-1, ip, for 4 d) decreased the LPS induced expression of MPC-1 mRNA by the ratios of 51 %, 70 %, 84 %, and 99 %, respectively (n = 6). CONCLUSION: In a dose-related fashion, CVPS-B inhibited the expression of MCP-1 mRNA induced by LPS in the rat splenocytes, but did not significantly affect the expression of MPC-1 mRNA in the normal rat.

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Effects of extracts of Coriolus versicolor (I’m-Yunity) on cell-cycle progression and expression of interleukins-1 beta,-6, and -8 in promyelocytic HL-60 leukemic cells and mitogenically stimulated and nonstimulated human lymphocytes.

TC Hsieh, J Kunichki, Z Darzynkiewicz, JM Wu.

Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, USA.

OBJECTIVE: The goal of this in vitro study was to test the cytostatic and cytotoxic activities of extracts derived from the polysaccharopeptide (PSP), I’m-Yunity (Integrated Chinese Medicine Holdings Ltd., Kowloon, Hong Kong) prepared from strain Cov-1 of the mushroom Coriolus versicolor. DESIGN: Different volumes of 70% ethanol and water extracts of I’m-Yunity were incubated with cultures of human promyelocytic leukemic HL-60 cells, and compared to nontreated control cells. At various times after treatment, cells were harvested and analyzed with respect to: (1). proliferation and cell cycle phase distribution, (2). induction of apoptosis, and (3). changes in expression of the immunomodulating cytokines interleukin (IL)-1 beta, IL-6, and IL-8. To test whether extracts also affected normal cells, similar experiments were also performed using isolated peripheral blood lymphocytes from healthy volunteers, with and without stimulation by the mitogen phytohemagglutinin (PHA). The ability of extracts to affect the secretion of IL-1 beta, IL-6, and IL-8 were assessed by enzyme-linked immunosorbent assay. RESULTS: HL-60 cells incubated with various amounts (1, 3, 5, 7.5, and 10 micro l/mL) of the extracts for 1-3 days showed dose-dependent, time-dependent growth suppression and decrease in cell viability. Flow cytometric analysis revealed partial cell arrest in the G(1) phase at less than 5 micro L/mL and induction of apoptosis at 10 micro L/mL or more of ethanol and water extracts, with the latter exhibiting more pronounced inhibition than the former. Experiments performed with lymphocytes demonstrated that extracts of I’m-Yunity alone were without effect; moreover, they also did not affect the lymphocyte response to PHA. Water extract of I’m-Yunity also significantly increased IL-1 beta and IL-6 while substantially lowering IL-8. CONCLUSIONS: I’m-Yunity acts selectively in HL-60 leukemic cells, resulting in cell cycle restriction through the G(1)/S checkpoint and the induction of apoptosis.

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Antioxidant properties of several medicinal mushrooms.

JL Mau, HC Lin, CC Chen.

Department of Food Science, National Chung-Hsing University, 250 Kuokuang Road, Taichung 402, Taiwan, Republic of China. jlmau@dragon.nchu.edu.tw

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.

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Tofung capsule (TFC) on the concentration neurotransmitter of blood active substance in brain and blood of migraine mice.

To research and influence the mechanism Tofung capsule (TFC) on the concentration of blood active substance and single amine neurotransmitter in brain and blood of migraine mice

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Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer.

KW Tsang, CL Lam, C Yan, JC Mak, GC Ooi, JC HO, B Lam, R Man, JS Sham, WK Lam.

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.

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