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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.

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.[…]

The cell death process of the anticancer agent polysaccharide-peptide (PSP) in human promyelocytic leukemic HL-60 cells.

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.[…]

Effects of polysaccharide peptide (PSP) from Coriolus versicolor on the pharmacokinetics of cyclophosphamide in the rat and cytotoxicity in HepG2 cells.

Chan SL, Yeung JH. Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China. cslkel@hotmail.com Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been shown to restore the immunological effects against cyclophosphamide-induced immuno-suppression, although the mechanism(s) involved remain uncertain. This study investigated the PSP-cyclophosphamide interaction by […]

Comparsion of Anti-cancer Effect between two kinds of Polysaccharide Peptide of Coriolus versicolor on Human Tumor Cell Lines in Vitro

PSK as a new immunomodulative drug had been widely used for clinical anticancer therapy in Japan. When combined with chemotherapy, radiotherapy and surgical operation, PSK is found to be able to improve the therapeutic effects. In 1983, a polysaccharide peptide of Coriolus versicolor Cov-1 was isolated from the mycelia by Qing-yao Yang. It is possessed of physio-chemical characteristics similar to PSK and designated as PSP. In the present study the anti-cancer effect of PSP was compared with PSK using four human tumor cell line targets in vitro.[…]

In vitro inhibition of proliferation of HL-60 cells by tetrandrine and coriolus versicolor peptide derived from Chinese medicinal herbs.

Coriolus versicolor polysaccharide peptide (CVP) and the bis-benzylisoquinoline alkaloids, tetrandrine (TET) and berbamine (BER), the active ingredients isolated from Chinese medicinal herbs known to possess antitumor activities, concentration-dependently inhibited the proliferation of human leukemic HL-60 cells. CVP did not affect the growth of normal human peripheral blood lymphocytes (PBL), whereas TET elicited concentration-dependent cytotoxic effects. Morphological observation and DNA analysis revealed that CVP elicited no effect on the morphological features of HL-60 cells and did not cause DNA fragmentation, but TET and BER caused cell shrinkage with the formation of apoptotic bodies, and showed clear evidence of DNA fragmentation. These findings indicate that TET and BER, but not CVP, inhibited the proliferation of HL-60 cells via induction of apoptosis.[…]

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.

Data on Krestin suggest that this family of drugs when used in combination with
radiotherapy, there might be an increase of the biological effects of radiation. To do a
pilot study on such a possibility, the authors have treated 41 moderate to advanced cases of
esophageal carcinoma with a combination of PSP and radiotherapy.[…]

Immune enhancement of a polysaccharides peptides isolated from Coriolus versicolor.

A protein-bound polysaccharides (PSP) isolated from Coriolus versicolor in Shanghai, at the concentrations of 100-800 micrograms/ml promoted lymphocyte proliferation. PSP 25 mg/kg ip into mice for 5 d antagonized the inhibition of IL-2 production by cyclophosphamide from activated T lymphocytes and restored the suppressed T-cell-mediated delayed, type hypersensitivity response to normal. PSP 10-1000 micrograms/ml induced interferon alpha and gamma production from human peripheral leukocytes 4 and 8 times respectively higher than that of the control groups. Moreover, PSP also increased phagocytic functions of host reticulo-endothelial system. The results suggest that the anti-tumor effects of PSP may be related to its potentiation of host immunological responses.[…]

Activation of peritoneal macrophages by polysaccharopeptide from the mushroom, Coriolus versicolor.

Polysaccharopeptide (PSP) is a substance produced by an edible mushroom, Coriolus versicolor which has been claimed to possess antitumor activity. However, neither tumoricidal activity nor cytotoxicity was observed when five tumor cell lines and mouse peritoneal macrophages were cultured in vitro in the presence of 2.5-10 micrograms/ml PSP. An increase in the production of reactive nitrogen intermediates, reactive oxygen intermediates (superoxide anions) and tumor necrosis factor was measured in peritoneal macrophages collected from inbred C57 mice which had received PSP in the drinking water for 2 weeks. Northern blot analysis also demonstrated that PSP activated the transcription of tumor necrosis factor gene in these cells, indicating that PSP exerted an immunomodulatory effect on the defensive cells.[…]

Effect of polysaccharide peptide (PSP) on glutathione and protection against paracetamol-induced hepatotoxicity in the rat.

The protective effects of polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, on paracetamol-induced hepatotoxicity was investigated in this study. The effect of PSP on hepatic glutathione status was also studied. PSP (300 mg/kg, i.p.) caused a 40% depletion of hepatic reduced glutathione (GSH) with a concomitant 50% increase in oxidized glutathione (GSSG), thus producing a 3-fold increase in the GSSG/GSH ratio. The PSP-induced GSH depletion itself had no hepatotoxic effects. PSP protected against paracetamol-induced hepatotoxicity by decreasing the paracetamol-induced elevation of serum glutamic-pyruvic transaminase (SGPT) activity from 511 +/- 71 U/ml to 187 +/- 58 U/ml (controls without paracetamol 105 +/- 4 U/ml) and serum glutamic-oxaloacetic transaminase (SGOT) activity from 462 +/- 63 to 152 +/- 48 U/ml (controls without paracetamol 54 +/- 6 U/ml). PSP did not reverse the depletion of total glutathione (GSH+GSSG) by the toxic dose of paracetamol. The GSSG/GSH ratio, which is a measure of oxidative stress, was significantly (p < 0.05) decreased when PSP was coadministered with paracetamol. PSP dose-dependently decreased the covalent binding of [14C]-paracetamol to microsomal proteins in vitro. When PSP was given to rats subchronically for 7 days (300 mg/kg/day, i.p.), the subsequent microsomes obtained also showed a 25% decrease in covalent binding to [14C]-paracetamol, suggesting that PSP interacted with the microsomal proteins rather than the chemically reactive metabolite of paracetamol. The changes in the binding affinity and capacity of the microsomal proteins by PSP may be related to its ability to alter the redox potential as indicated by the effects of PSP on the GSSG/GSH status.[…]

Immunomodulatory and antitumor activities of a polysaccharide-peptide complex from a mycelial culture of Tricholoma sp., a local edible mushroom.

A polysaccharide-peptide complex (PSPC) with immunomodulatory and antitumor activities was obtained from a submerged mycelial culture of Tricholoma sp., a local edible mushroom. The polysaccharide-peptide complex exhibited a molecular weight of 17 K in gel filtration and a single band after SDS-polyacrylamide gel electrophoresis. It was characterized by non-adsorption on both DEAE-Sepharose CL-6B and CM-cellulose. It could activate the macrophages, stimulate the proliferation of T-cells, and inhibit the growth of sarcoma 180 in mice. It possessed more potent immunomodulatory and antitumor activities than Coriolus versicolor polysaccharopeptide (PSP) and deserves to be studied as a potential agent for immunomodulation and cancer therapy.[…]