Ho Cheong-Yip, Kim Chi-Fai, Leung Kwok-Nam, Fung Kwok-Pui, Tse Tak-Fu, Chan Helen, Lau Clara Bik-San
School of Pharmacy, The Chinese University of Hong Kong, Hong Kong, PR China.
Oncol Rep. 2006 Sep;16(3):609-16.
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.
云芝,又称杂色云芝,已被证明对多种癌细胞具有抗肿瘤作用。我们之前的研究表明,从云芝制备的标准化水乙醇提取物通过诱导凋亡抑制人白血病细胞的增殖。本研究旨在通过调节人早幼粒细胞白血病(HL-60)细胞系中Bax、Bcl-2和细胞色素c蛋白的表达来评估凋亡的潜在机制,以及使用无胸腺小鼠异种移植模型评估云芝提取物作为抗白血病药物的潜力。我们的结果表明,云芝提取物剂量依赖性地抑制HL-60细胞的增殖(IC50 = 150.6微克/毫升),凋亡细胞的核小体产量增加。在用云芝提取物处理的HL-60细胞中,促凋亡蛋白Bax的表达显著上调,尤其是在16和24小时后。同时,抗凋亡蛋白Bcl-2的表达随之下调,这表现为Bax/Bcl-2比值增加。孵育24小时后,云芝提取物显著但短暂地促进了细胞色素c从线粒体释放到细胞质中。在无胸腺裸鼠异种移植模型中的体内研究也证实了云芝提取物对人白血病细胞的生长抑制活性。总之,云芝提取物在体内和体外可能通过线粒体途径诱导凋亡来减弱人白血病细胞的增殖。云芝提取物可能对某些形式的人类白血病治疗具有重要价值。