Tag Archives: coriolus versicolor psp

Cancer, Immunotherapy, Leukemia, Medical Studies, PSP, Tumor

The culture duration affects the immunomodulatory and anticancer effect of polysaccharopeptide derived from Coriolus versicolor

Cheuk-Lun Lee, Xiaotong Yang, Jennifer Man-Fan Wan

Department of Zoology, Kardoorie Biological Science Building, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China

Received 24 December 2003; accepted 5 October 2004

Abstract

Polysaccharopeptide (PSP) derives from the medicinal mushroom Coriolus versicolor is considered a biological response modifier with potential pharmaceutical applications. Significant literatures support the immune and anticancer functions of PSP; however, standardization is of big concern because variable biotechnological factors can affect both the chemical and biological properties of PSP. In this study, the extracts of PSP obtained at different days from the Coriolus versicolor culture were tested in vitro for their immune function on human normal peripheral blood mononuclear cells (PBMC) and cytotoxicity on the human leukemia Molt 4 cells. Over the 10-days culture period, both biomass and peptide/polysaccharide content were increased with time. The increase in proliferation index of PBMC and their production of interleukin 1 beta (IL-1_), tumor necrosis factor alpha (TNF-_) and gamma interferon (IFN-_) in the presence of PHA strengthens the correlation between culture duration and biological potency of PSP. The growth inhibition of the Molt 4 cells by PSP also depended on its maturity. Flow cytometry analysis on cell cycle and cell death (apoptosis) of Molt 4 cells indicated that the anticancer mechanism of PSP is related to its ability to induce S-phase cell arrest and apoptosis, respectively. Together, these results suggest that monitor the harvest duration is critical for the quality control of polysaccharopeptide in the biotechnological industry.

© 2005 Elsevier Inc. All rights reserved. Keywords: Coriolus versicolor; Polysaccharopeptide; Flow cytometry; High performance liquid chromatography; Peripheral blood mononuclear cells; Molt 4

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in vitro, Medical Studies, PSP, Tumor

Study on Anti-tumor Action of PSP

R.T. Chen, A.M. Zhou, B. Xu Department of Pharmacology I Shanghai Institute of Materia Medica, Academia Sinica

Abstract

It has been reported that some polysaccharides possess antitumor action. PSP is a glycopeptide isolated from Coriolus versicolor by Yang et al. Its physiological properties have been investigated. In the present work we studied the antitumor action of PSP in vitro experiments.

Summary

PSP at the doses of 500 or 1000ug/ml produced inhibitory effect on P388 luekemia cells by 79-96%. At the dose of 1000 or 2000ug/ml PSP caused the inhibition of [3H]UR or [3H]TdR incorporation into RNA and DNA in Ehrlich ascites carcinoma cells was found to be the inhibition rate 50-80% or 27-47% respectively.

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Cancer, Chemotherapy, Medical Studies, Melanoma, PSP

The Preliminary Appraisal of Polysaccharide Peptide (PSP) in Malignant and Non-malignant Diseases

Z.Y. Sun et al Shanghai Medical University

Abstract

28 late cases of malignancy of all pathologically proven were evaluated. Among them are one case of melanoma, two cases of non-Hodgkin lymphoma (NHL), twenty cases of gastro-intestinal cancers, three cases of bronchogenic carcinoma, one case each of primary hepatocellular carcinoma and multiple peritoneal malignancies of unknown origin respectively.

Most of the cases had surgery, irradiation or anticancer chemotherapy in combination. PSP were taken orally in capsules, total dose ranged from 20g to more than 800g.

A case of malignant melanoma of back was operated for five times, she was operated for the first time in Jan 1982, lymphadenopathy of right iliac and inguired glands began, consequently wide dissections of the involved nodes were done. In August 1983, the disease metastatized to right chest wall and st. axillary glands and resected specimen showed one of three subseapular nodes and one of the eight axillary nodes were metastatic melanoma lesions, the estrogen receptor content of the specimen was 125F mol/mg. On September 10, the same year a total hysterectomy was done. She received 7 courses of CCNU, PCZ and VCR regime beginning from October 1983. Despite the stable condition of her disease, she had to give up further chemotherapy on account of distinct leucopenia. In April 1985, she was found to have GI bleeding, GI bladder, condition improved after Tamoxifen and symphomate treatments. Half year later melana reappeared and right hemicolectomy and partial resection of the jijunum were done. PSP was given postoperatively, and there was no chemotherapy for already more than 2 years. She is apparently well and can participate ordinary heavy work without difficulty.

Another case of multiple peritoneal metastasis of unknown origin was benefited by PSP also. She had mass of 5x5cm in RLQ of abdomen and quite massive ascites. Ager 100g

of PSP, ascites disappeared and the mass decreased to 3x3cm. White count went up to 5200 from 3800, lymphocytic mitosis increased from 28 to 36%.

Two cases of NHL were apparently benefited too by PSP in spite of the fact one each had received systemic chemotherapy and radiotherapy of waldegers ring respectively.

All the 28 cases except 2, the general conclitims of patients and appetite improved 2/3 of the cases showed an increase of white count of 1000 at least. Around half of the patients had an increased of function of cellular immunity. One case of liver cancer showed marked amelioration of abdominal pain 80 that he could abandon dolantin injection and one case of lung cancer had conspicuous decrease of the malignant pleural effusion.

Five cases of chronic gastrites and three cases of chronic active hepatitis showed remarkable improvement in symptoms and liver function test. HBsAg declined in two of three hepatitis patients.

So far no adverse drug reaction has been observed, there were no impairment of liver and renal functions after the long term administration of PSP even up to years.

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Clinical Trials, Lymphocytes, Medical Studies, PSP

The Physio-Chemical Characteristics of the Polysaccharide-peptide (PSP) of Coriolus versicolor (Yun Zhi)

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Q.Y. Yang, S.C. Yong and X.T. Yang

Shanghai Normal University

Abstract

PSP is an anticarcinogen and immunological regulator identified as a polysaccharide peptide which has been extracted from the deep layer cultivated mycelia of Coriolus versicolor. Infrared spectrophotometer at wavelenghts of 3432 cm-1, 1621 cm-1 and 1073 cm-1 produces three absorption bands.

The N.M.R. of PSP has the characteristic to show absorption at 1.0-2.5 ppm, 3.0-3.4, 4.5, 5.4 ppm and broad absorption in the region of 3.0-4.3 ppm.

Use spectrophotometer to determine the effluent separated from the column of gel chromatography (Sephadex G-75), The results shown that maximum absorption peaks of polypeptide and polysaccharides are found in the homeo-collecting tubes.

The polysaccharide portion is composed of the five monsaccharides, galactose, glucose, mannose, xylose, and fucose. The amino acids most frequently found in the polypeptide are aspartic and glutamic. PSP has no sharply defined fusion point. It is insoluble in methyl alcohol, pryridine, benzene, hexane, and chloroform but is very soluble in hot water. The pH value of its 1% water solution is 6.6. It is heat and light stable. &nbp; When kept at a temperature of 100oC for 48 hours or irradiated with ultraviolet light for 30 hours there is essentially no change in composition. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) the molecular weight has been calculated at about 1×105 Dalton.

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Cancer, Medical Studies, PSP

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

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

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

Abstract

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.

PMID: 15870943 [PubMed – indexed for MEDLINE]

PubMed

U.S. National Library of Medicine

National Institutes of Health

Publication Types, MeSH Terms, Substances

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in vitro, Medical Studies, PSK, PSP

PSP and PSK

Informatioin Office of the Research Institute of Fungi Shanghai Teachers University

PSP and PSK are the 2 products of Yun Zhi ratified by Chinese Ministry of Public Health and Japanese Ministry of Public Health respectively.

PSK was first manufactured by Kureha Chemical Industry Co. Ltd. The PS in PSK represents polysaccharide and K represents the first alphabet of the name of this Company. It was originally written as PS-K and was later changed to PSK. o; The commercial name of the product is Krestin.

PSP was prepared by Professor Qing-yao Yang. It is like PSK and is also a kind of compound polysaccharide. On the molecules of the polysaccharide, the small molecular protein (polypeptide) is connected. So it is called Yun Zhi Duo Tang Tai or Yun Zhi Tang Tai. The Tang Tai English names were originally glycopeptide, proteoglucan, glycosaminoglucan, etc. But the polysaccharide is all composed of N-acetyl-amino-hexose. But the polysaccharides of PSP and PSK are not composed of N-acetylamino-hexose. So it is not suitable to use the name. So the word “polysaccharopeptide” or “polysaccharide-peptide” is used and is abbreviated as PSP or Ps-p.

According to the different degrees of extraction, there are a series of PSP products. PSP directly extracted from the mycelia of Yun Zhi is called Yun Zhi Polysaccharide-peptide (Trade mark Qing Kang) and PSP polysacchardie-peptide (Landford). The former is sold on the market of Mainland China and the latter is according to the export specifications and is sold overseas. These 2 products are mainly used for tumorous patients.

The essence of the product is obtained by further isolation of the crude product. It is called Essence of Mushroom (Yun Zhi) (The sole distributor is Winsor Health Products Ltd., Hong Kong) used for healthy purposes.

Japan is quite specialized in the research of Yun Zhi. Besides PSK, Hirose, S. et al, (1970), Naruse S. and Takeda S. (in 1970) and Sugiura M. (in 1980) isolated two anticancerous components of the mycelia of Yun Zhi respectively. The former is called

ASTO and latter D–II. In addition, Ito H. et al (in 1974) extracted from the fermented mash of Yun Zhi an anti-tumor component which does not contain protein and it is called Coriolan. Its chemical components are glucans (by Hayashida S. et al, in 1992). But the above-mentioned three components still remain in the process of pharmacological research and was not used in clinical application.

Though PSP and PSK are all a kind of protein bound polysaccharide and are all extracted from the deep layer cultivated mycelia, yet they use the different strains, fermented medium and different extracted methods. Thus there is a certain difference between PSP and PSK. It is known that in the polysaccharide of PSP there is fucose, while there is no fucose in PSP, which contains arabinose and rhamnose; while there are no such ingredients in PSK. On the other hand, according to the pharmacological and clinical research, PSP has the definite effect of alleviating pain and increasing appetite, while there is no such report on PSK. Comparison of Two Characterisitics of PSP and PSK

Items compared

Similarities

Dissimilarities

Fungi

Yun Zhi Coriolus versicolor (Fr.) Quel

PSP: Cov-1 strain PSK: CM-101 strain

Drug produced

PSP: capsule PSK: loose package

Powder color

brown

PSP: brown PSK: dark brown

Raw materials

deep-layer cultivated mycelia (2N)

Fermentation technology

with glucose as the main carbon source (25oC, 3 days)

PSP: nitrogenous source: soya beancake powder PSK: nitrogenous source: peptone and yeast cake

Extract and isolate

obtained by immersion in hot water

PSP: isolate by alcoholic precipitation PSK: isolate by salting out with (NH4)2SO4

Medicinal ingredients

protein bound polysaccharide; average molecular wt. 1 x 105 Da the polysaccharide is formed from many monosaccahrides containing

PSP: polysaccharides contain arabinose and rhmanose, but no fucose PSK: polysaccharides do not

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Cancer, Medical Studies, PSP

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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Medical Studies, PSP, Tumor

Fungal polysaccharopeptide inhibits tumor angiogenesis and tumor growth in mice.

JC Ho, MA Konerding, A Gaumann, M Groth, WK Liu.

Department of Anatomy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.

Angiogenesis is crucial to tumor growth and metastasis, and interruption of this process is a prime avenue for therapeutic intervention of tumor proliferation. The present study has made use of the S180 tumor-bearing mouse model to investigate the polysaccharopeptide, PSP, isolated from the edible mushroom Coriolus versicolor, a herbal medicine known for its anti-angiogenesis properties. Quantitative analysis of microcorrosion casting of the tumor tissue showed more angiogenic features such as dense sinusoids and hot spots, in control (untreated) than in PSP-treated animals. Immunostaining of tumor tissues with antibody against the endothelial cell marker (Factor VIII) demonstrated a positive correlation in that both the vascular density and tumor weight were lower in mice treated with PSP. Morphometric analysis of corrosion casts revealed that, even though the total amount of new vessel production was reduced, the basic tumor type-specific vascular architecture was retained. However, the expression of vascular endothelial cell growth factor (VEGF) in these tumors was suppressed. In conclusion, anti-angiogenesis should be one of the pathways through which PSP mediated its anti-tumor activity.

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Cancer, Immunotherapy, in vitro, Leukemia, Medical Studies, PSP

Molecular characterization of Coriolus versicolor PSP-induced apoptosis in human promyelotic leukemic HL-60 cells using cDNA microarray.

F Zeng, CC Hon, WH Sit, KY Chow, RK Hui, IK Law, VW Ng, XT Yang, FC Leung, JM Wan.

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

Proteins and peptide bound polysaccharides (PSP) extracted from Basidiomycetous fungi are widely used in cancer immunotherapy and recently demonstrated to induce apoptosis in cancer cells in vitro. In order to provide the molecular pharmacological mechanisms of PSP on human cancer cells, we investigated the gene expression profiles of PSP-treated apoptotic human promyelotic leukemic HL-60 cells using ResGen 40k IMAGE printed cDNA microarray. In total 378 and 111 transcripts were identified as differentially expressed in the apoptotic cells by at least a factor of 2 or 3, respectively. Our data show that PSP-induced apoptosis in HL-60 cells might be mediated by up-regulation of early transcription factors such as AP-1, EGR1, IER2 and IER5, and down-regulation of NF-kappaB transcription pathways. Other gene expression changes, including the increase of several apoptotic or anti-proliferation genes, such as GADD45A/B and TUSC2, and the decrease of a batch of phosphatase and kinase genes, may also provide further evidences in supporting the process of PSP induced apoptosis in cancer cells. Some of the well-characterized carcinogenesis-related gene transcripts such as SAT, DCT, Melan-A, uPA and cyclin E1 were also alternated by PSP in the HL-60 cells. These transcripts can be employed as markers for quality control of PSP products on functional levels. The present study provides new insight into the molecular mechanisms involved in PSP-induced apoptosis in leukemic HL-60 cells analyzed by cDNA microarray.

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Cancer, Leukemia, Medical Studies, PSP, Tumor

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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