Anti-cancer and anti-angiogenic effects of curcumin and tetrahydrocurcumin on implanted hepatocellular carcinoma in nude mice  

作　　者：Pornprom Yoysungnoen Ponthip Wirachwong Chatchawan Changtam Apichart Suksamrarn Suthiluk Patumraj 

机构地区：[1]Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand [2]The Government Pharmaceutical Organization, Rama VI, Rajtevi, Bangkok 10300, Thailand [3]Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand [4]Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10300, Thailand

出　　处：《World Journal of Gastroenterology》2008年第13期2003-2009,共7页世界胃肠病学杂志（英文版）

基　　金：The Thailand Research Fund, No. MRG4980032;partially supported by The National Center for Genetic Engineering and Biotechnology, Thailand

摘　　要：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.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 ×10^6 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.

关 键 词：Tumor angiogenesis HepG2 CURCUMIN TETRAHYDROCURCUMIN Intravital fluorescence videomicroscopy 

分 类 号：R735.7[医药卫生—肿瘤]