School of Pharmacy, The Chinese University of Hong Kong, Hong Kong, PR China.
Abstract
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 microg/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.
Dept of Clinical Pharmacy, University of California, San Francisco, CA 94143, USA. ps01459@itsa.ucsf.edu
Abstract
The inhibition or induction of hepatic cytochrome P450 3A4 (CYP3A4) enzyme associated with herbal medicines such as I’m-Yunity (Coriolus versicolor) can result in clinically significant herb-drug interactions. The active ingredient of I’m-Yunity is believed to be polysaccharopeptide polymer (PSP). Drug interactions between I’m-Yunity and other medications or supplements are yet to be investigated. The objective of this single-treatment, one-period, three-phase, open-labeled study was to evaluate the ability of I’m-Yunity to inhibit or induce CYP3A4 in 12 healthy adult volunteers (8 women and 4 men) aged between 23 and 54 years through the use of a CYP3A4-specific assay, the erythromycin breath test (EBT). EBT measurements are reported as percentage of 14C-Erythromycin metabolized/hr. Participants were given a 14-day supply of I’m-Yunity and instructed to take 1200 mg, three times daily with meals. Comparisons of all subjects’ mean CYP3A4 activities were performed with the EBT before and after taking I’m- Yunity. Results revealed a mean EBT change (SD) from baseline of 0.08% (0.56%) 14C-Erythromycin metabolized/hr, which was not significant (p = 0.63). Therefore, 14 days of exposure to I’m-Yunity was not associated with clinically significant CYP3A4 inhibition or induction, suggesting that short-term administration of I’m-Yunity with medications primarily metabolized by CYP3A4 is safe and not expected to be associated with significant herb-drug interactions. However, it is still unknown whether interactions exist between I’m-Yunity and other medications metabolized by other CYP450 isozymes or enzyme/transporter systems.
Department of Immunology, Institute for Biological Research Sinisa Stankovi?, Belgrade University, Belgrade, Serbia.
Abstract
Numerous studies have shown immunostimulatory and anti-tumor effects of water and standardized aqueous ethanol extracts derived from the medicinal mushroom, Coriolus versicolor, but the biological activity of methanol extracts has not been examined so far. In the present study we investigated the anti-tumor effect of C. versicolor methanol extract (which contains terpenoids and polyphenols) on B16 mouse melanoma cells both in vitro and in vivo. In vitro treatment of the cells with the methanol extract (25-1600 microg/ml) reduced melanoma cell viability in a dose-dependent manner. Furthermore, in the presence of the methanol extract (200 microg/ml, concentration IC(50)) the proliferation of B16 cells was arrested in the G(0)/G(1) phase of the cell cycle, followed by both apoptotic and secondary necrotic cell death. In vivo methanol extract treatment (i.p. 50 mg/kg, for 14 days) inhibited tumor growth in C57BL/6 mice inoculated with syngeneic B16 tumor cells. Moreover, peritoneal macrophages collected 21 days after tumor implantation from methanol extract-treated animals exerted stronger tumoristatic activity ex vivo than macrophages from control melanoma-bearing mice. Taken together, our results demonstrate that C. versicolor methanol extract exerts pronounced anti-melanoma activity, both directly through antiproliferative and cytotoxic effects on tumor cells and indirectly through promotion of macrophage anti-tumor activity.