Antitumor activity of novel fluoro-substituted (–)-epigallocatechin-3-gallate analogs

Epidemiological studies support the cancer-preventive effects of green tea and its main constituent (–)-epigallocatechin gallate [(–)-EGCG], however, (–)-EGCG is unstable under physiological conditions. Here we report that two novel fluoro-substituted (–)-EGCG analogs inhibited tumor growth with similar potency to that of Pro-EGCG (1) which has improved potency over parental compound (–)-EGCG in human breast cancer MDA-MB-231 xenografts. MDA-MB-231 tumors treated with each fluoro-substituted (–)-EGCG analog showed proteasome inhibition and apoptotic cell death, suggesting that the proteasome might be one of the cellular targets of fluoro-(–)-EGCGs and that proteasome inhibition is partially responsible for the observed antitumor activity.