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.