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.
Category Archives: Leukemia
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.
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
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
Stimulation of interferon-gamma-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction.
Display Settings: Abstract
Anticancer Res. 1990 Jan-Feb;10(1):55-8.
Kim F, Sakagami H, Tanuma S, Konno K.
First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.
PSK, a protein-bound polysaccharide extracted from the mycelia of Coriolus versicolor (Fr.) Quel, stimulated tumor
necrosis factor-induced cytotoxicity against mouse L-929 fibroblast. PSK also stimulated interferon-gamma-induced
differentiation of human myelogenous leukemic U-937 and THP-1 cells. The differentiated cells had higher proportions of
cells that expressed NBT-reducing activity and alpha-naphthyl acetate esterase activity. Among four PSK subfractions, the
highest molecular weight fraction (MW greater than 200 kD) had the most potent stimulating activity. This is the first report
regarding direct PSK modulation of cytokine action.
PMID: 2110432 [PubMed – indexed for MEDLINE]
Stimulation of human peripheral blood polymorphonuclear cell iodination by PSK subfractions.
Display Settings: Abstract
Anticancer Res. 1990 May-Jun;10(3):697-702.
Sakagami H, Kim F, Konno K.
First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.
A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr.) Quel, stimulated the
iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear
cells (PMN), human promyelocytic leukemic HL-60 cells and human myeloblastic leukemic ML-1 cells. In contrast, PSK did
not significantly increase the iodination of other cultured cell lines (U-937, THP-1, L-929, T98G, BALB 3T3). The PSK
stimulation of iodination of both PMN and HL-60 cells depended on incubation time and temperature, and was significantly
suppressed by the presence of myeloperoxidase inhibitors. Among various PSK subfractions, the highest molecular weight
fraction (MW greater than 200 kD), or the fraction precipitated at pH 4.0-4.5, stimulated the iodination most. In contrast,
natural and chemically modified glucans had little or no stimulation activity. The active PSK subfractions synergistically
enhanced TNF stimulation of PMN iodination. The data suggest the presence of some unique components in PSK which
directly stimulate the iodination of myeloperoxidase-positive cells.
PMID: 2369086 [PubMed – indexed for MEDLINE]
U.S. National Library of Medicine
National Institutes of Health
Publication Types, MeSH Terms, Substances
Effects of extracts of Coriolus versicolor (I’m-Yunity) on cell-cycle progression and expression of interleukins-1 beta,-6, and -8 in promyelocytic HL-60 leukemic cells and mitogenically stimulated and nonstimulated human lymphocytes.
TC Hsieh, J Kunichki, Z Darzynkiewicz, JM Wu.
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, USA.
OBJECTIVE: The goal of this in vitro study was to test the cytostatic and cytotoxic activities of extracts derived from the polysaccharopeptide (PSP), I’m-Yunity (Integrated Chinese Medicine Holdings Ltd., Kowloon, Hong Kong) prepared from strain Cov-1 of the mushroom Coriolus versicolor. DESIGN: Different volumes of 70% ethanol and water extracts of I’m-Yunity were incubated with cultures of human promyelocytic leukemic HL-60 cells, and compared to nontreated control cells. At various times after treatment, cells were harvested and analyzed with respect to: (1). proliferation and cell cycle phase distribution, (2). induction of apoptosis, and (3). changes in expression of the immunomodulating cytokines interleukin (IL)-1 beta, IL-6, and IL-8. To test whether extracts also affected normal cells, similar experiments were also performed using isolated peripheral blood lymphocytes from healthy volunteers, with and without stimulation by the mitogen phytohemagglutinin (PHA). The ability of extracts to affect the secretion of IL-1 beta, IL-6, and IL-8 were assessed by enzyme-linked immunosorbent assay. RESULTS: HL-60 cells incubated with various amounts (1, 3, 5, 7.5, and 10 micro l/mL) of the extracts for 1-3 days showed dose-dependent, time-dependent growth suppression and decrease in cell viability. Flow cytometric analysis revealed partial cell arrest in the G(1) phase at less than 5 micro L/mL and induction of apoptosis at 10 micro L/mL or more of ethanol and water extracts, with the latter exhibiting more pronounced inhibition than the former. Experiments performed with lymphocytes demonstrated that extracts of I’m-Yunity alone were without effect; moreover, they also did not affect the lymphocyte response to PHA. Water extract of I’m-Yunity also significantly increased IL-1 beta and IL-6 while substantially lowering IL-8. CONCLUSIONS: I’m-Yunity acts selectively in HL-60 leukemic cells, resulting in cell cycle restriction through the G(1)/S checkpoint and the induction of apoptosis.
Cytotoxic activities of Coriolus versicolor (Yunzhi) extract on human leukemia and lymphoma cells by induction of apoptosis.
CB Lau, CY Ho, CF Kim, KN Leung, KP Fung, TF Tse, HH Chan, MS Chow.
School of Pharmacy, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. email@example.com
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 microg/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 +/- 15.2 microg/ml), Raji (253.8 +/- 60.7 microg/ml) and NB-4 (269.3 +/- 12.4 microg/ml). The extract however did not exert any significant cytotoxic effect on normal liver cell line WRL (IC50 > 800 microg/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. Copyright 2004 Elsevier Inc.
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.
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.
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.