Inhibitory effect of dehydroabietylamine-fluorobenzaldehyde on human hepatocellular carcinoma cells
- Author:
Ling LIU
1
Author Information
- Publication Type:Journal Article
- Keywords: 1-(7-isopropyl-1, 4a-dimethyl-1, 2, 3, 4, 4a, 9, 10, 10a-octahydrophenanthren-l-yl) -N-(4-fluorobenzylidene) methanamine; Apoptosis; Dehydroabietylamine- fluorobenzaldehyde; Hepatocellular carcinoma; Mitochondria
- From: Chinese Pharmaceutical Journal 2013;48(4):269-274
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To examine the anti-proliferation effects of a novel derivative of dehydroabietylamine, dehydroabietyl-amine-fluorobenzaldehyde[1-(7-isopropyl-1, 4a-dimethyl -1, 2, 3, 4, 4a, 9, 10, 10a-octahydrophenanthren-l-yl)-N- (4-fluorobenzyli-dene) methanamine, DHAA-F]. on human hepatocellular carcinoma cells and to expolore its molecular mechanism. METHODS: MTT assay was adopted to detect the proliferation status of the cells treated with DHAA-F; cellular apoptosis and reduction of mitochondria membrane potential (δφm) were analyzed using flow cytometry (FCM): Western blotting assay was used to evaluate the release of Cyt c, and the expressions of p53, Bcl-2 and Bax protein; and the caspase-3activity was determined with fluorescence spectrophotometry. To evaluate the anti-tumor effect of DHAA-F in vivo, mouse model bearing inoculated H22 tumor was established. RESULTS: DHAA-F strongly inhibited human hepatoma cells proliferation. The IC50 value of DHAA-F was (44.47±2.15) pjnol · L-1 for SMMC-7721, (48.64±1.76) μmol · L-1 for Bel-7402, and (52.83±2.25) μmmol · L-1 for HepG2. DHAA-F displayed a significant inhibitory effect on the growth of SMMC-7721cells in a dose- and time-dependent manner. When SMMC-7721 cells were pretreated with DHAA-F for 24 h, the apoptosis rate significantly increase and the mitochondrial membrane potential significantly decreased. Western blotting assay showed significant decrease of Bcl-2 protein expression and increase of Bax, p53 protein expression, cytosol Cyt c level and caspase-3activity. DHAA-F could significantly reduce tumor weight in the H22 solid tumor mouse model in vivo. CONCLUSION: These findings suggest that DHAA-F has potent antitumor activity both in vivo and in vitro and the mechanism may be related to the apoptosis induced by DHAA-F through a mitochondrial pathway.
