Liver Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Apr 7, 2008; 14(13): 2003-2009
Published online Apr 7, 2008. doi: 10.3748/wjg.14.2003
Anti-cancer and anti-angiogenic effects of curcumin and tetrahydrocurcumin on implanted hepatocellular carcinoma in nude mice
Pornprom Yoysungnoen, Ponthip Wirachwong, Chatchawan Changtam, Apichart Suksamrarn, Suthiluk Patumraj
Pornprom Yoysungnoen, Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand
Ponthip Wirachwong, The Government Pharmaceutical Organization, Rama VI, Rajtevi, Bangkok 10300, Thailand
Chatchawan Changtam, Apichart Suksamrarn, Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand
Suthiluk Patumraj, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10300, Thailand
Author contributions: Yoysungnoen P and Patumraj S designed research; Yoysungnoen P performed research; Wirachwong P contributed HepG2 cell lines; Changtam C and Suksamrarn A prepared curcumin and its analog; Yoysungnoen P and Patumraj S analyzed data; and Yoysungnoen P and Patumraj S wrote the paper.
Correspondence to: Pornprom Yoysungnoen, Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand. hi_aor@yahoo.com
Telephone: +66-81-7009474
Fax: +66-55-261197
Received: December 10, 2007
Revised: February 21, 2008
Published online: April 7, 2008
Abstract

AIM: To determine the effect of tetrahydrocurcumin (THC) on tumor angiogenesis compared with curcumin (CUR) by using both in vitro and in vivo models of human hepatocellular carcinoma cell line (HepG2).

METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay was used for testing the anti-proliferating activities of CUR and THC. In male BALB/c nude mice, 2 × 106 human HepG2 cells were inoculated onto a dorsal skin-fold chamber. One day after HepG2 inoculation, the experimental groups were fed oral daily with CUR or THC (300 mg/kg or 3000 mg/kg). On d 7, 14 and 21, the tumor microvasculature was observed using fluorescence videomicroscopy and capillary vascularity (CV) was measured.

RESULTS: Pathological angiogenic features including microvascular dilatation, tortuosity, and hyper-permeability were observed. CUR and THC could attenuate these pathologic features. In HepG2-groups, the CV were significantly increased on d 7 (52.43%), 14 (69.17%), and 21 (74.08%), as compared to controls (33.04%, P < 0.001). Treatment with CUR and THC resulted in significant decrease in the CV (P < 0.005 and P < 0.001, respectively). In particular, the anti-angiogenic effects of CUR and THC were dose-dependent manner. However, the beneficial effect of THC treatment than CUR was observed, in particular, from the 21 d CV (44.96% and 52.86%, P < 0.05).

CONCLUSION: THC expressed its anti-angiogenesis without any cytotoxic activities to HepG2 cells even at the highest doses. It is suggested that anti-angiogenic properties of CUR and THC represent a common potential mechanism for their anti-cancer actions.

Keywords: Tumor angiogenesis, HepG2, Curcumin, Tetrahydrocurcumin, Intravital fluorescence videomicro-scopy