CHEONG-YIP HO, CHI-FAI KIM, KWOK-NAM LEUNG, KWOK-PUI FUNG, TAK-FU TSE, HELEN CHAN and CLARA BIK-SAN LAU
Coriolus versicolor (CV), also called Yunzhi, has been demonstrated to exert anti-tumor effects on various types of cancer cells. Our previous studies have demonstrated that a standardized aqueous ethanol extract prepared from CV inhibited the proliferation of human leukemia cells via induction of apoptosis. The present study aimed to evaluate the underlying mechanisms of apoptosis through modulation of Bax, Bcl-2 and cytochrome c protein expressions in a human pro-myelocytic leukemia (HL-60) cell line, as well as the potential of the CV extract as anti-leukemia agent using the athymic mouse xenograft model. Our results demonstrated that the CV extract dose-dependently suppressed the proliferation of HL-60 cells (IC50=150.6 ?g/ml), with increased nucleosome production from apoptotic cells. Expression of pro-apoptotic protein Bax was significantly up-regulated in HL-60 cells treated with the CV extract, especially after 16 and 24 h. Meanwhile, expression of anti-apoptotic protein Bcl-2 was concomitantly down-regulated, as reflected by the increased Bax/Bcl-2 ratio. The CV extract markedly, but transiently, promoted the release of cytochrome c from mitochondria to cytosol after 24-h incubation. In vivo studies in the athymic nude mouse xenograft model also confirmed the growth-inhibitory activity of the CV extract on human leukemia cells. In conclusion, the CV extract attenuated the human leukemia cell proliferation in vivo, and in vitro possibly by inducing apoptosis through the mitochondrial pathway. The CV extract is likely to be valuable for the treatment of some forms of human leukemia.
Full article: https://mushroomstudies.co/wp-content/uploads/2010/09/Coriolus-versicolor-Yunzhi-extract-attenuates-growth-of-human-leukemia-xenografts-and-induces-apoptosis-through-the-mitochondrial-pathway.pdf
School of Pharmacy, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Abstract
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.
PMID: 15908782 [PubMed – indexed for MEDLINE]Free Article
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Abstract
Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been previously shown to have immuno-stimulatory, anti-tumour and analgesic effects in animal models. When used as an adjunct in cancer chemotherapy in clinical trials carried out in China, PSP improved the quality of life in the patients by improving appetite and alleviating symptoms associated with cancer chemotherapy. In this study, the effects of non-toxic doses of PSP on phase I metabolism was investigated in the rat, using the conventional probe antipyrine. Acute PSP (3-5 micromol/kg, i.p.) treatment did not produce significant changes in antipyrine clearance. Sub-chronic treatment with PSP (1-3 micromol/kg/day, i.p., 3 days) decreased the antipyrine clearance (30-35%), with an increase in the plasma half-life (T1/2) by 55% and an increase in the area under concentration-time curve (AUC) by 61%. Total hepatic cytochrome P450 (P450) was dose-dependently decreased (32-54%) after sub-chronic, but not the acute treatment of PSP. Given that PSP can affect phase I metabolism and hepatic cytochrome P450 content, the concomitant use of PSP with other therapeutic agents that undergo phase I metabolism should be carefully monitored.