Tag Archives: in vivo

Chemopreventive Effect of PSP Through Targeting of Prostate Cancer Stem Cell-Like Population

Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.

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Polysaccharopeptide from Coriolus versicolor has potential for use against human immunodeficiency virus type 1 infection

Polysaccharopeptide (PSP) isolated from the edible mushroom Coriolus versicolor was tested for its potential as an anti-human immunodeficiency virus type 1 (HIV-1) compound in a series of in vitro assays. It demonstrated inhibition of the interaction between HIV-1 gp 120 and immobilized CD4 receptor (IC50=150 microgram/ml), potent inhibition of recombinant HIV-1 reverse transcriptase (IC50=6.25 microgram/ml), and inhibited a glycohydrolase enzyme associated with viral glycosylation. These properties, coupled with its high solubility in water, heat-stability and low cytotoxicity, make it a useful compound for further studies on its possible use as an anti-viral agent in vivo.

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Clinical trial China phase 2

Polysaccharide-peptide (PSP) is a protein bound polysaccharide isolated from the COV-1 strain of Yunzhi (Coriolous versicolor mushroom) and made from modern alcohol extraction techniques. Each capsule contains 0.34 grams of PSP. Experimental in-vitro and in-vivo studies have shown PSP inhibits the proliferation of cancer cells including P338 leukemia cells, S 180 cells, Ehrlich ascites, and stomach and lung cancer cells. It also inhibits the growth of some tumors such as the lymphatic tumor of human skin tissue cells. In addition, PSP affects the immune system of mice by stimulating the production of ?\interferons, increasing the phagocytic index and metabolic rate of the reticuloendothilial system and by raising the HC 50 (median hemolytic dose), IgG and PFC (plaque forming cell) values. Human in-vivo experiments have also shown PSP can modulate the immune system by helping to prevent and partly eliminate the side effects of radiation and chemotherapeutic agents used by cancer patients.

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Clinical trail China phase 1

Polysaccharide-peptide (PSP) is a protein bound polysaccharides isolated from the COV-1 strain of Yunzhi (Coriolous versicolor mushroom) and made from modern alcohol extraction techniques. Each capsule contains 0.34 grams of PSP. Experimental in-vitro and in-vivo studies have shown PSP inhibits the proliferation of cancer cells including P338 leukemia cells, S 180 cells, Ehrlich ascites, and stomach and lung cancer cells. It also inhibits the growth of some tumors such as the lymphatic tumor of human skin tissue cells. In addition, PSP affects the immune system of mice by stimulating the production of ?\interferons, increasing the phagocytic index and metabolic rate of the reticuloendothilial system and by raising the HC 50 (median hemolytic dose), IgG and PFC (plaque forming cell) values. Human in-vivo experiments have also shown PSP can modulate the immune system by helping to prevent and partly eliminate the side effects of radiation and chemotherapeutic agents used by cancer patients.

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Suppression of in vivo tumor-induced angiogenesis by the protein-bound polysaccharide PSK.

U.S. National Library of Medicine

National Institutes of Health

In Vivo. 1994 Mar-Apr;8(2):247-50.

Kanoh T, Matsunaga K, Saito K, Fujii T.

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

Abstract

The anti-angiogenic effects of an antitumor protein-bound polysaccharide, PSK, obtained from cultured mycelia of Coriolus

versicolor in basidiomycetes were examined by the mouse dorsal air sac assay. PSK suppressed the mouse hepatoma

MH134-induced angiogenesis when assessed by morphological and biochemical examinations. This finding suggested that

the anti-metastatic effect of PSK is attributed to the suppression of tumor-induced angiogenesis.

PMID: 7522606 [PubMed – indexed for MEDLINE]

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Clinical Experience in the Use of PSP

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

Abstract

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.

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Morphological and biochemical alterations of macrophages produced by a glycan, PSK.

Morphological and biochemical alterations of macrophages produced by a glycan, PSK.

Kamisato JK, Nowakowski M.

Department of Pathology, SUNY Health Science Center, Brooklyn 11203.

Abstract

A glycan extracted from Coriolus versicolor (PSK, Krestin) which has antitumor and immunomodulator properties produced marked morphological and biochemical changes when added to cultures of mouse peritoneal macrophages. The cells were more spread and elongated than in control cultures, and these changes were accompanied by alterations in the rate of protein and DNA synthesis. In PSK-treated murine peritoneal macrophages the rate of protein synthesis increased above the level seen in control cultures after two days and reached a level twenty-fold higher than control on day four; this elevated rate of protein synthesis was maintained throughout the seven-day observation period. DNA synthesis was induced after four days in the presence of PSK, and reached a level ten-fold higher than control baseline on day five. This induction of DNA synthesis, however, could not be attributed to a mitogenic activity on lymphocytes. The alterations caused by PSK in macrophage metabolism may be related to the immunomodulating and antitumor activities of PSK in vivo.

PMID: 3204014 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/3204014

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

Effect of polysaccharide peptide (PSP) on in vivo sulphation and glucuronidation of paracetamol in the rat.

Yeung JH, Chiu LC, Ooi VE.

Department of Pharmacology, Chinese University of Hong Kong, Shatin.

Abstract

The effect of polysaccharide peptide (PSP), an immunomodulator isolated from Coriolus versicolor COV-1, on the disposition of paracetamol was investigated in the rat. PSP (100 and 200 mg/kg, i.v.) was administered 30 min before a moderate dose (100 mg/kg, i.v.) of paracetamol was given. Plasma and bile concentrations of paracetamol, paracetamol glucuronide and paracetamol sulphate were measured by high performance liquid chromatography. The pharmacokinetics of paracetamol (100 mg/kg) alone was consistent with those reported previously, using a one-compartment model. PSP (200 mg/kg) significantly (P < 0.05) increased the clearance (controls, 19.06 +/- 2.74 ml/min/kg: PSP treated, 26.22 +/- 0.84 ml/min/kg) and volume of distribution (controls, 1.35 +/- 0.11 l/kg: PSP treated, 1.61 +/- 0.04 l/kg) of paracetamol by 37% and 21%, respectively. These changes were associated with concomitant increases in the glucuronide and sulphate metabolites in plasma, with significant increases in the Cmax and Tmax for both metabolites. The biliary excretion rate of paracetamol glucuronide and paracetamol sulphate were also measured. The Cmax values of paracetamol sulphate were significantly (P < 0.01) increased by 2.4-fold from 907.8 +/- 157.7 micrograms/ml (controls) to 3061 +/- 331 micrograms/ml after PSP treatment. The lower dose of PSP (100 mg/kg) had no significant effect on the disposition of paracetamol in this study, which agreed with previous reports that a low dose of PSP (100-200 mg/kg, i.p.) was less effective in the protection against paracetamol-induced hepatotoxicity. The time course of the increase in paracetamol sulphate in plasma and bile in this study coincided with the transient perturbation of glutathione (GSH) turnover by a similar dose range of PSP previously described, such that more cysteine was available for oxidation to inorganic sulphate. This increase in sulphate conjugation by PSP would, in part, contribute to the increase in disposition of paracetamol and may be related to the ability of PSP to decrease the covalent binding of paracetamol to microsomal proteins previously reported. Further studies are necessary to understand the mechanism(s) involved in the PSP-induced increases in paracetamol glucuronide and paracetamol sulphate formation and biliary excretion.

PMID: 8983934 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/8983934

Effects of Coriolus versicolor polysaccharides on superoxide dismutase activities in mice.

Wei WS, Tan JQ, Guo F, Ghen HS, Zhou ZY, Zhang ZH, Gui L.

Department of Pharmacology, Second Military Medical University, Shanghai, China.

Abstract

AIM: To study if Coriolus versicolor polysaccharides (CVP) influence the superoxide dismutase (SOD) activities in mice.

METHODS: Normal, tumor-bearing, and radiated ICR mice were injected ip with CVP daily for 3-15 d. The SOD activity was assayed by epinephrine autoxidation test.

RESULTS: The SOD activities in lymphocytes and thymus were increased by CVP in both the normal mice with or without delayed hypersensitivity (DH). In tumor-bearing mice, CVP exerted not only inhibitory effects on tumor, growth and SOD activity in tumor tissue but also complete or partial restorative effects on the suppressed DH and on the declined SOD activities in lymphocytes, spleen, and thymus. The total SOD and manganese-containing SOD (MnSOD) activities in lymphocytes and thymus were dose-dependently enhanced by CVP (5-20 mg.kg-1) on d 3 after the tumor transplantation. In the mice exposed to 60Co (3 or 6 Gy), DH and SOD activities were dose-dependently decreased. These changes were completely or partly prevented by CVP.

CONCLUSION: CVP exerted the favorable effects on SOD activities in mice. Coriolus versicolor polysaccharides (CVP) exert inhibitory effects on experimental and clinical tumors. These effects are presumed to be mediated mainly by host-defence mechanism, especially immunological responeses. Superoxide dismutase (SOD) plays an important role in protecting cells against superoxide radical (O2-.) damages and over-production of O2-. or SOD abnormities exist in many diseases. The present study was to investigate if the CVP could exert some favorable effects on SOD activities in vivo.

PMID: 9772673 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/9772673