Gastric Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 7, 2006; 12(1): 21-28
Published online Jan 7, 2006. doi: 10.3748/wjg.v12.i1.21
Berberine induces cell cycle arrest and apoptosis in human gastric carcinoma SNU-5 cell line
Jing-Pin Lin, Jai-Sing Yang, Jau-Hong Lee, Wen-Tsong Hsieh, Jing-Gung Chung
Jing-Pin Lin, School of Chinese Medicine, China Medical University, Taichung City 404, Taiwan, China
Jai-Sing Yang, Department of Medical Technology, Yuan-Pei University of Science and Technology, Hsinchu City, 300, Taiwan, China
Jau-Hong Lee, Department of Surgery, China Medical University Hospital, Taichung City, 404, Taiwan, China
Wen-Tsong Hsieh, Department of Pharmacology, China Medical University, Taichung City 404, Taiwan, China
Jing-Gung Chung, Department of Microbiology, School of Biological Science and Technology, China Medical University, Taichung City 404, Taiwan, China
Co-first-authors: Jing-Pin Lin and Jai-Sing Yang
Co-correspondent: Jing-Pin Lin
Supported by The Grant CMU92-CM-02 from China Medical University
Correspondence to: Dr Jing-Gung Chung, Department of Microbiology, School of Biological Science and Technology, China Medical University, 91 Hsueh-Shih Road, Taichung 404, Taiwan. China. jgchung@mail.cmu.edu.tw
Telephone: +886-4-2205-3366 Fax: +886-4-2205-3764
Received: July 5, 2005
Revised: July 8, 2005
Accepted: July 20, 2005
Published online: January 7, 2006
Abstract

AIM: To investigate the relationship between the inhibited growth (cytotoxic activity) of berberine and apoptotic pathway with its molecular mechanism of action.

METHODS: The in vitro cytotoxic techniques were complemented by cell cycle analysis and determination of sub-G1 for apoptosis in human gastric carcinoma SNU-5 cells. Percentage of viable cells, cell cycle, and sub-G1 group (apoptosis) were examined and determined by the flow cytometric methods. The associated proteins for cell cycle arrest and apoptosis were examined by Western blotting.

RESULTS: For SNU-5 cell line, the IC (50) was found to be 48 μmol/L of berberine. In SNU-5 cells treated with 25-200 μmol/L berberine, G2/M cell cycle arrest was observed which was associated with a marked increment of the expression of p53, Wee1 and CDk1 proteins and decreased cyclin B. A concentration-dependent decrease of cells in G0/G1 phase and an increase in G2/M phase were detected. In addition, apoptosis detected as sub-G0 cell population in cell cycle measurement was proved in 25-200 μmol/L berberine-treated cells by monitoring the apoptotic pathway. Apoptosis was identified by sub-G0 cell population, and upregulation of Bax, downregulation of Bcl-2, release of Ca2+, decreased the mitochondrial membrane potential and then led to the release of mitochondrial cytochrome C into the cytoplasm and caused the activation of caspase-3, and finally led to the occurrence of apoptosis.

CONCLUSION: Berberine induces p53 expression and leads to the decrease of the mitochondrial membrane potential, Cytochrome C release and activation of caspase-3 for the induction of apoptosis.

Keywords: Berberine; Cell cycle; Apoptosis; Caspase-3; ROS; MMP; SNU-5 cells