Cancer Prevention by Green Tea via EGCG-Mediated Inhibition of Fatty Acid Synthase

Summary

Green tea is widely accepted to lower the risk of developing cancer, including hormone-responsive cancers, but the precise mechanism of its cancer-preventive effect is not fully understood. Recently, the green tea component epigallocatechin-3-gallate (EGCG) was demonstrated to inhibit in-vitro enzymatic activity of chicken liver fatty acid synthase (FAS), an enzyme that is frequently overexpressed in many epithelial tumors. Since chemical FAS inhibitors such as cerulenin and C75 are known to inhibit growth and to induce apoptosis of several cancer cell lines in vitro and tumor xenografts in vivo, it was investigated whether EGCG also inhibited FAS activity in cultured prostate cancer (PCA) cells in vivo and how this inhibition affected lipogenesis, cell proliferation, and cell viability. EGCG significantly inhibited FAS activity in PCA cells (with high FAS expression levels). This FAS inhibition was paralleled by decreased lipogenesis, growth inhibition, and apoptosis. In contrast, epicatechin, another closely related catechin that does not influence FAS activity, had no effect on PCA cell proliferation or survival. EGCG also inhibited FAS activity and proliferation of normal fibroblasts (with low FAS expression), but did not induce fibroblast apoptosis. Taken together, it can be concluded that EGCG efficiently inhibits FAS in cultured cells, and specifically induces apoptosis in PCA cells but not in normal fibroblasts, thereby providing interesting perspectives for using EGCG in antineoplastic therapies.