Brief Article
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World J Gastroenterol. Jun 21, 2011; 17(23): 2848-2854
Published online Jun 21, 2011. doi: 10.3748/wjg.v17.i23.2848
Effects of sargentgloryvine stem extracts on HepG-2 cells in vitro and in vivo
Ming-Hua Wang, Min Long, Bao-Yi Zhu, Shu-Hui Yang, Ji-Hong Ren, Hui-Zhong Zhang
Ming-Hua Wang, Min Long, Bao-Yi Zhu, Shu-Hui Yang, Ji-Hong Ren, Hui-Zhong Zhang, Department of Laboratory Medicine and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi Province, China
Author contributions: Wang MH and Long M contributed equally to this work; Wang MH and Long M designed the study, prepared the Sargentgloryvine stem extract, performed the statistical analysis and drafted the manuscript; Zhu BY performed the animal model studies; Yang SH performed the protein expression studies; Ren JH conducted the flow cytometry; Zhang HZ conceived the study and also participated in the study design and coordination; all authors have read and approved the final manuscript.
Supported by National Science and Technology Key Project for the Development of New Drugs in China, No. 2009ZX09103-422
Correspondence to: Hui-Zhong Zhang, MD, PhD, Department of Laboratory Medicine and Research Center, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, Xi’an 710038, Shaanxi Province, China. zhz328@yahoo.com.cn
Telephone: +86-29-84777470 Fax: +86-29-84777654
Received: January 24, 2011
Revised: February 24, 2011
Accepted: March 3, 2011
Published online: June 21, 2011
Abstract

AIM: To observe the effects of sargentgloryvine stem extracts (SSE) on the hepatoma cell line HepG-2 in vitro and in vivo and determine its mechanisms of action.

METHODS: Cultured HepG-2 cells treated with SSE were analysed by 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-Diphenyltetrazolium bromide and clone formation assay. The cell cycle and apoptosis analysis were conducted by flow cytometric, TdT-Mediated dUTP Nick End Labeling and acridine orange/ethidium bromide staining methods, and protein expression was examined by both reverse transcriptase-polymerase chain reaction and Western blotting. The pathological changes of the tumor cells were observed by haematoxylin and eosin staining. Tumor growth inhibition and side effects were determined in a xenograft mouse model.

RESULTS: SSE treatment could not only inhibit HepG-2 cell proliferation in a dose- and time-dependent manner but also induce apoptosis and cell cycle arrest at the S phase. The number of colonies formed by SSE-treated tumor cells was fewer than that of the controls (P < 0.05). SSE induced caspase-dependent apoptosis accompanied by a significant decrease in Bcl-xl and Mcl-1 and elevation of Bak expression (P < 0.05). Tumor necrosis factor α in the xenograft tumor tissue and the liver functions of SSE-treated mice showed no significant changes at week 8 compared with the control group (P > 0.05). Systemic administration of SSE could inhibit the HepG-2 xenograft tumor growth with no obvious toxic side effects on normal tissues.

CONCLUSION: SSE can induce apoptosis of HepG-2 cells in vitro and in vivo through decreasing expression of Bcl-xl and Mcl-1 and increasing expression of Bax.

Keywords: Sargentgloryvine stem extract, Apoptosis, Human hepatocellular carcinoma, HepG-2, Bcl-2 family