Tag Archives: antitumor

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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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.

KP Hui, WH Sit, JM Wan.

Department of Zoology, The University of Hong Kong, Pokfulam Road, Hong Kong, SAR, P.R. China.

Activation of the cell death program (apoptosis) is a strategy for the treatment of human cancer, and unfortunately a large number of drugs identified as cell cycle-specific agents for killing cancer cells are also toxic to normal cells. The present study demonstrates that the polysaccharide peptide (PSP) extracted from the Chinese medicinal mushroom, Coriolus versicolor, used in combination therapy in China, has the ability to lower the cytotoxicity of certain anti-leukemic drugs via their interaction with cell cycle-dependent and apoptotic pathways. Flow cytometry analysis demonstrated that pre-treatment of PSP (25-100 microg/ml) dose-dependently enhanced the cell cycle perturbation and apoptotic activity of doxorubicin (Doxo) and etoposide (VP-16), but not cytarabine (Ara-C) in human promyelocytic leukemia HL-60 cells. The antagonistic result from combined treatment with Ara-C and PSP may be caused by the removal of HL-60 cells in the G1-S boundary by PSP before exposure to Ara-C. A negative correlation between the increase in apoptotic cell population (pre-G1 peak) with the S-phase cell population expression (R2=0.998), the expression of cyclin E expression (R2=0.872) and caspase 3 activity (R2=0.997) suggests that PSP enhanced the apoptotic machinery of Doxo and VP-16 in a cell cycle-dependent manner and is mediated, at least in part, by the PSP-mediated modulation of the regulatory checkpoint cyclin E and caspase 3. This study is the first to describe the cell cycle mechanistic action of PSP and its interaction with other anticancer agents. Our data support the potential development of PSP as an adjuvant for leukemia treatment, but also imply the importance of understanding its interaction with individual anticancer agents.

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Enhancement of the antitumor effect by the concurrent use of a monoclonal antibody and the protein-bound polysaccharide PSK in mice bearing a human cancer cell line.

Kanoh T, Saito K, Matsunaga K, Oguchi Y, Taniguchi N, Endoh H, Yoshimura M, Fujii T, Yoshikumi C.

Kureha Chemical Ind. Co., Ltd., Biomedical Research Laboratories, Tokyo, Japan.

Abstract

The antitumor effects of a monoclonal antibody against a human cancer cell line and a protein-bound polysaccharide, PSK, obtained from cultured mycelia of Coriolus versicolor in basidiomycetes were examined. The IgG2a monoclonal antibody against the human colon cancer cell line colo 205 induced in vitro antibody-dependent macrophage-mediated cytotoxicity against the cancer cells, but only slightly suppressed the in vivo growth of the cancer cells. Concurrent use of PSK with the antibody enhanced the in vitro antibody-dependent macrophage-mediated cytotoxicity as well as the in vivo antitumor activity. These findings suggest that the combined use of a monoclonal antibody and PSK, which have different modes of action, may be useful in the treatment of cancer.

PMID: 7919129 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/7919129

Differential anti-tumor activity of coriolus versicolor (Yunzhi) extract through p53- and/or Bcl-2-dependent apoptotic pathway in human breast cancer cells.

CY Ho, CF Kim, KN Leung, KP Fung, TF Tse, H Chan, CB Lau.

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.

Cytotoxic activities of Coriolus versicolor (Yunzhi) extract on human leukemia and lymphoma cells by induction of apoptosis

C.B.S. Laua, C.Y. Hoa, C.F. Kima, K.N. Leungb, K.P. Fungb, T.F. Tsec, H.H.L. Chanc, M.S.S. Chowa

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 Ag/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 F 15.2 Ag/ml), Raji (253.8 F 60.7 Ag/ml) and NB-4 (269.3 F 12.4 Ag/ml). The extract however did not exert any significant cytotoxic effect on normal liver cell line WRL (IC50 > 800 Ag/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.

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CLONING OF SEQUENCES INDUCED AND SUPPRESSED BY ADMINISTRATION OF PSK, ANTITUMOR PROTEIN-BOUND POLYSACCHARIDE

Kunitaka Hirose, Michinori Hakozaki, Kenichi Matsunaga, Chikao Yoshikumi, Tetsuya Hotta, Masaaki Yanagisawa, Mikio Yamamoto, Hideya Endo.

To elucidate the effects of PSK, a protein-bound polysaccharide from Coriolus versicolor, on gene expression in tumor cells, we prepared cDNA clone libraries from PSKtreated and untreated cells of a rat ascites hepatoma line, AH66, which was previously shown to be susceptible to the antitumor action of this compound. Two PSK-induced and one suppressed cDNA clones were selected from these libraries by using a differential colony hybridization and RNA blot hybridization. PSK was thus shown to have a direct effect on the transcription and consequently on the translation of tumor cells.

Full article: http://mushroomstudies.co/wp-content/uploads/2010/09/Cloning-of-sequences-induced-and-suppressed-by-administration-of-PSK-antitumor-protein-bound-polysaccharide.pdf

Clinical study of biological response modifiers as maintenance therapy for hepatocellular carcinoma.

Suto T, Fukuda S, Moriya N, Watanabe Y, Sasaki D, Yoshida Y, Sakata Y.

We conducted a randomized, controlled trial comparing 5-fluorouracil (5-FU) with or without biological response modifiers (BRMs) as a maintenance therapy for hepatocellular carcinoma (HCC) after treatment with percutaneous ethanol injection (PEI), transcatheter arterial embolization (TAE) or arterial infusion of antitumor agents (AI). A total of 58 cases of HCC were classified into 4 groups as follows: group I, PSK with 5-FU (n = 15); group II, lentinan with 5-FU (n = 15); group III, OK-432 with 5-FU (n = 12); and group IV, 5-FU alone as the control (n = 16). The mean survival time, mortality rate, time to progression, and T4/T8 ratio of lymphocytes in the peripheral blood were compared among the four groups. There was no significant difference in the background factors among the groups. In group I, the T4/T8 ratio of lymphocytes was reduced after the therapy. No significant difference was found among the groups in terms of the mean survival time, mortality rate, or time to progression. PEI for initial therapy was superior to the other therapies in terms of the mean survival time and mortality rate. These results suggest that the addition of BRM to maintenance therapy with 5-FU exerts no prognostic benefit on HCC patients treated with PEI, TAE, or AI.

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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