Liver Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 14, 2006; 12(6): 874-879
Published online Feb 14, 2006. doi: 10.3748/wjg.v12.i6.874
Anti-hepatoma activity and mechanism of ursolic acid and its derivatives isolated from Aralia decaisneana
Ze Tian, Geng Lin, Rui-Xia Zheng, Feng Huang, Meng-Su Yang, Pei-Gen Xiao
Ze Tian, Geng Lin, Rui-Xia Zheng, Feng Huang, Pei-Gen Xiao, Department of Pharmacology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China
Meng-Su Yang, Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong, China
Co-correspondence: Pei-Gen Xiao
Supported by the National Natural Science Foundation of China, No. 30470195
Correspondence to: Ze Tian, Associate Professor of Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. zetian603@hotmail.com
Telephone: +86-10-62894597 Fax: +86-10-62894597
Received: July 17, 2005
Revised: July 23, 2005
Accepted: July 29, 2005
Published online: February 14, 2006
Abstract

AIM: To investigate the anti-tumor activity of ursolic acid (UA) and its derivatives isolated from Aralia decaisneana on hepatocellular carcinoma both in vitro and in vivo.

METHODS: In vivo cytotoxicity was first screened by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Morphological observation, DNA ladder, flow cytometry analysis, Western blot and real time PCR were employed to elucidate the cytotoxic mechanism of UA. Implanted mouse hepatoma H22 was used to evaluate the growth inhibitory effect of UA in vivo.

RESULTS: UA could significantly inhibit the proliferation of HepG2 and its drug-resistance strain, R-HepG2 cells, but had no inhibitory effect on primarily cultured normal mouse hepatocytes whereas all the six derivatives of UA could not inhibit the growth of all tested cell lines. Further study on mechanism demonstrated that apoptosis and G0/G1 arrest were involved in the cytotoxicity and cleavage of poly-(ADP-ribose)-polymerase (PARP). Downregulation of cyclooxygenase-2 (COX-2) protein and upregulation of heat shock protein (HSP) 105 mRNA correlated to the apoptosis of HepG2 cells treated with UA. In addition, UA also could inhibit the growth of H22 hepatoma in vivo.

CONCLUSION: UA is a promising anti-tumor agent, but further work needs to be done to improve its solubility.

Keywords: Aralia decaisneana; Ursolic acid; Hepatoma