Cancer, Leukemia, Medical Studies, PSP

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

X Yang, WH Sit, DK Chan, JM Wan.

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

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.

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Breast Cancer, Cancer, Chemotherapy, in vitro, Medical Studies

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.

School of Pharmacy, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

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.

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Cancer, Medical Studies, Tumor

Lack of prevention of large intestinal cancer by VPS, an extract of Coriolus versicolor mushroom.

M Coles, B Toth.

Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Cancer prevention studies were conducted with VPS, a hot water extract of the Coriolus versicolor (CV) mushroom, in female Swiss mice. The extract was administered in the diet for life to the animals. Three groups of mice received the following treatments: a). 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) was administered as 10 weekly subcutaneous injections of 20 microg/g body weight, starting at 9 weeks of age; b). VPS was given at a 2% dose level starting at 7 weeks of age followed by 1,2-DMH, as described in group a; c). 1,2-DMH was administered as described in group a followed by VPS at a 2% dose level starting at 21 weeks of age. The number of animals with large intestinal tumors and the total number of these tumors were: a). 30,321; b). 29,359; and c). 28,415. These differences are not statistically significant. Because extracts of the CV mushroom are used by cancer patients as nutritional supplements in the U.S., and particularly in the Orient, the present negative result should caution its users.

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Medical Studies, PSP

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 studying the effects of PSP on the pharmacokinetic of cyclophosphamide in the rat and the effect of PSP on the cytotoxic effects of cyclophosphamide on a cancer cell line (HepG2 cells). In the pharmacokinetic studies in the rat, acute pre-treatment of PSP (4 micromol/kg/day, i.p.) decreased the clearance (CL) of cyclophosphamide by 31%, with a concomitant increase in the area under concentration-time curve (AUC) by 44%, and prolongation of the plasma half-life (T(1/2)) by 43%. Sub-chronic pre-treatment of PSP (2 micromol/kg/day, i.p., 3 days) decreased the CL of cyclophosphamide by 33%, with a concomitant increase in the AUC by 50%, and prolongation of the plasma T(1/2) by 34%. In cytotoxicity studies using HepG2 cells, non-toxic dose of PSP (1-10 microM) enhanced the cytotoxicity of cyclophosphamide. PSP at 10 microM further decreased HepG2 cell viability by 22% compared to when cyclophosphamide was present alone. In summary, PSP enhanced the cytotoxic effect of cyclophosphamide on a cancer cell line in vitro and altered the pharmacokinetics of cyclophosphamide in vivo in the rat. Both of these effects may be beneficial in the use of PSP as an adjunct to cyclophosphamide treatment.

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Leukemia, Medical Studies

Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and extracellular signaling regulatory protein expression by water extracts of I’m-Yunity™ (PSP)

Published: 11 September 2006
BMC Complementary and Alternative Medicine 2006, 6:30 doi:10.1186/1472-6882-6-30
Received: 13 April 2006
Accepted: 11 September 2006
This article is available from: http://www.biomedcentral.com/1472-6882/6/30
© 2006 Hsieh et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: I’m-Yunity™ (PSP) is a mushroom extract derived from deep-layer cultivated mycelia of the patented Cov-1 strain of Coriolus versicolor (CV), which contains as its main bioactive ingredient a family of polysaccharo-peptide with heterogeneous charge properties and molecular sizes. I’m-Yunity™ (PSP) is used as a dietary supplement by cancer patients and by individuals diagnosed with various chronic diseases. Laboratory studies have shown that I’m-Yunity™ (PSP) enhances immune functions and also modulates cellular responses to external challenges. Recently, I’m-Yunity™ (PSP) was also reported to exert potent anti-tumorigenic effects, evident by suppression of cell proliferation and induction of apoptosis in malignant cells. We investigate the mechanisms by which I’m-Yunity™ (PSP) elicits these effects.

 

Methods: Human leukemia HL-60 and U-937 cells were incubated with increasing doses of aqueous extracts of I’m-Yunity™ (PSP). Control and treated cells were harvested at various times and analyzed for changes in: (1) cell proliferation and viability, (2) cell cycle phase transition, (3) induction of apoptosis, (4) expression of cell cycle, apoptogenic/anti-apoptotic, and extracellular regulatory proteins.

 

Results: Aqueous extracts of I’m-Yunity™ (PSP) inhibited cell proliferation and induced apoptosis in HL- 60 and U-937 cells, accompanied by a cell type-dependent disruption of the G1/S and G2/M phases of cell cycle progression. A more pronounced growth suppression was observed in treated HL-60 cells, which was correlated with time- and dose-dependent down regulation of the retinoblastoma protein Rb, diminution in the expression of anti-apoptotic proteins bcl-2 and survivin, increase in apoptogenic proteins bax and cytochrome c, and cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa truncated product. Moreover, I’m-Yunity™ (PSP)-treated HL-60 cells also showed a substantial decrease in p65 and to a lesser degree p50 forms of transcription factor NF-?B, which was accompanied by a reduction in the expression of cyclooxygenase 2 (COX2). I’m-Yunity™ (PSP) also elicited an increase in STAT1 (signal transducer and activator of transcription) and correspondingly, decrease in the expression of activated form of ERK (extracellular signal-regulated kinase).

 

Conclusion: Aqueous extracts of I’m-Yunity™ (PSP) induces cell cycle arrest and alterations in the\ expression of apoptogenic/anti-apoptotic and extracellular signaling regulatory proteins in human leukemia cells, the net result being suppression of proliferation and increase in apoptosis. These findings may contribute to the reported clinical and overall health effects of I’m-Yunity™ (PSP).

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Cancer, in vitro, Medical Studies, PSK, PSP, Types Of Extract

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

L.Z. Xu Laboratory of Pathology Cancer Institute, Shanghai Medical University

Abstract

In the present study the anti-cancer effect of polysaccharide peptide of Coriolus versicolor Cov-1 (PSP) was compared with polysaccharide peptide of Coriolus versicolor CM-101 (PSK) on four human tumor cell line targets (SGC 7901, stomach cancer cell; SPC, human lung adenocarcinoma cell; SLY, human monocytic leukemia cell and Mei, human skin histiocytic lymphoma cell) in Vitro.

PSP had similar cytotoxic effects upon human tumor cells as PSK, both inhibiting cell growth. In comparison with control specimens, the SPC cell line treated with PSP (1000ug/ml) for 72 hours at 37oC showed marked morphological changes such as cell swelling, chromatin aggregation, formation of polynuclear cells and sawtooth on the surface of cell nuclei.

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.

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Medical Studies, PSP

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

Y Dong, MM Yang, CY Kwan.

Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong.

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.

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Immunotherapy, Medical Studies

Polysaccharopeptide from the mushroom Coriolus versicolor possesses analgesic activity but does not produce adverse effects on female reproductive or embryonic development in mice.

TB Ng, WY Chan.

Departments of Biochemistry and Anatomy, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong.

Coriolus versicolor polysaccharopeptide has been reported to exert immunomodulatory and antitumor actions. The present study showed that it exhibits analgesic activity in the hot-plate test upon intraperitoneal administration to ICR mice. 2. It did not affect ovarian steroidogenesis, ovulation and midterm gestation in mice. It did not exert an adverse effect on mouse embryonic development either, as evidenced by the lack of an effect on somite number, axial length and the incidence of abnormalities in heartbeat, yolk sac circulation, optic vesicle, otic vesicle, shape of body axis, forelimb buds, branchial apparatus, cranial neural tube and head size. 3. Its analgesic activity would add to its attribute as an immunomodulatory and antitumor drug.

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Cancer, Chemotherapy, Immunotherapy, Medical Studies

Treatment of cancer with mushroom products.

JA Monro.

Breakspear Hospital, Hemel Hempstead, Herts, United Kingdom. jmonro@breakspearmedical.com

Cancer has been attributed to 3 causes: pollution, infection, and poor nutrition. Conventional treatments include surgery, chemotherapy, and radiotherapy. The author proposes that immunotherapy also be considered. Among other environmental influences, dietary deficiencies and carcinogenic viral infections must be investigated and treated wherever possible. It has been suggested that mushrooms, in particular, have a structure that is immunomodulatory because it resembles the proteoglycan structure in the human extracellular matrix, and both are metabolically active. Inasmuch as mitochondria have a bacterial origin, proteoglycans may have a mushroom origin. The author describes a study which shows that natural killer cells can double in number with 8 wk of treatment with Coriolus versicolor. Also described is an epidemiological survey of cancer deaths among Flammulina velutipes farmers in Japan, which found that the mushroom farmers had lower rates of cancer deaths than controls who were not involved in mushroom farming?

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Cancer, in vitro, Medical Studies, PSK, PSP

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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