Liver Cancer
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 15, 2004; 10(20): 2944-2948
Published online Oct 15, 2004. doi: 10.3748/wjg.v10.i20.2944
Down-modulation of heat shock protein 70 and up-modulation of Caspase-3 during schisandrin B-induced apoptosis in human hepatoma SMMC-7721 cells
Yi-Feng Wu, Ming-Fu Cao, Yan-Ping Gao, Fei Chen, Tao Wang, Edward P. Zumbika, Kai-Xian Qian
Yi-Feng Wu, Yan-Ping Gao, Kai-Xian Qian, College of Life Sciences, Zhejiang University, Hangzhou 310027, Zhejiang Province, China
Ming-Fu Cao, College of Life Sciences, Hangzhou Teachers college, Hangzhou 310012, Zhejiang Province, China
Fei Chen, Tao Wang, Edward P. Zumbika, School of Medicine, Zhejiang University, Hangzhou 310027, Zhejiang Province, China
Author contributions: All authors contributed equally to the work.
Supported by the National Key Technologies Research and Development Program of China during the 10th Five-Year Plan Period, No. 2002BA760C
Correspondence to: Kai-Xian Qian, College of Life Sciences, Zhejiang University, Hangzhou 310027, Zhejiang Province,China. biocell@zju.edu.cn
Telephone: +86-571-87952761
Received: February 2, 2004
Revised: February 16, 2004
Accepted: February 21, 2004
Published online: October 15, 2004
Abstract

AIM: To investigate the effect of schisandrin B (Sch B) on proliferation and apoptosis of human hepatoma SMMC-7721 cells in vitro and regulation of Hsp70 and Caspases-3, 7, 9 expression by Sch B.

METHODS: Human hepatoma cell line SMMC-7721 was cultured and treated with Sch B at various concentrations. Growth suppression was detected with MTT colorimetric assay. Cell apoptosis was confirmed by DNA ladder detection and flow cytometric analysis. The expression of Hsp70, Caspases-3, 7, 9 were analyzed by Western blot analysis.

RESULTS: Sch B inhibited the growth of hepatoma SMMC-7721 cells in a dose-dependent manner, leading to a 50% decrease in cell number (LC50) value of 23.50 mg/L. Treatment with Sch B resulted in degradation of chromosomal DNA into small internucleosomal fragments, evidenced by the formation of a 180-200 bp DNA ladder on agarose gels. FCM analysis showed the peak areas of subdiploid at the increased concentration of Sch B. The results of Western bolt analysis showed that Hsp70 was down-regulated and Caspase-3 was up-regulated, while the activity of Caspases-7, -9 had no significant change.

CONCLUSION: Sch B is able to inhibit the proliferation of human hepatoma SMMC-7721 cells and induce apoptosis, which goes through Caspase-3-dependent and Caspase-9-independent pathway accompanied with the down-regulation of Hsp70 protein expression at an early event.

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