Impact of farnesyl-O-acetylhydroquinone ether on the growth of implanted B16 melanoma in mice.

摘要

The Mevalonate pathway provides essential intermediates for cell growth. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is the rate-limiting enzyme in the mevalonate pathway. Farnesol, a 15-carbon sesquiterpene, triggers the degradation of HMG CoA reductase and suppresses the growth of tumor cells and tumors in animals. However, farnesol is vulnerable to oxidative activities in vivo and limited in its anti-tumor activity. In the current study we seek to test the safety and efficacy of a novel farnesol derivative, farnesyl-O-acetylhydroquinone ether, resistant to such oxidative activities. In the safety study, three groups (n = 10) of mice were fed AIN-93G diet supplemented with 0, 1, and 10 mmol farnesyl-O-acetylhydroquinone respectively for forty nine days. No adverse effects was observed in the group fed 1 mmol farnesyl-O-acetylhydroquinone/kg diet, whereas significant weight loss was observed in the group fed 10 mmol farnesyl-O-acetylhydroquinone/kg diet. In the efficacy study, two groups of mice (n = 20) were put on AIN-93G diet supplemented with 0 and 1 mmol farnesyl-O-acetylhydroquinone respectively following implantation of B16 melanoma cells. Average tumor weight in the experimental group was 23% lower than that of the control group, even though the difference was not significant by a repeated measure ANOVA analysis.