title: Epigallocatechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells.
abstract: Chemical inhibitors of fatty acid synthase (FAS) inhibit growth and induce apoptosis in several cancer cell lines in vitro and in tumor xenografts in vivo. Recently the green tea component epigallocatechin-3-gallate (EGCG) was shown to act as a natural inhibitor of FAS in chicken liver extracts. Here we investigated whether EGCG inhibits FAS activity in cultured prostate cancer cells and how this inhibition affects endogenous lipid synthesis, cell proliferation and cell viability. The high levels of FAS activity in LNCaP cells were dose-dependently inhibited by EGCG and this inhibition was paralleled by decreased endogenous lipid synthesis, inhibition of cell growth and induction of apoptosis. In contrast, epicatechin (EC), another closely related green tea polyphenolic compound, which does not inhibit FAS, had no effect on LNCaP cell growth or viability. Treatment of nonmalignant cells with low levels of FAS activity (fibroblasts) with EGCG led to a decrease in growth rate but not to induction of apoptosis. These data indicate that EGCG inhibits FAS activity as efficiently as presently known synthetic inhibitors and selectively causes apoptosis in LNCaP cells but not in nontumoral fibroblasts. These findings establish EGCG as a potent natural inhibitor of FAS in intact cells and strengthen the molecular basis for the use of EGCG as a chemopreventive and therapeutic antineoplastic agent.
authors.affiliation: Laboratory for Experimental Medicine and Endocrinology, Department of Developmental Biology, Gasthuisberg, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Brusselmans
authors.forename: Ellen
authors.initials: E
authors.lastname: De Schrijver
authors.forename: Walter
authors.initials: W
authors.lastname: Heyns
authors.forename: Guido
authors.initials: G
authors.lastname: Verhoeven
authors.forename: Johannes V
authors.initials: JV
authors.lastname: Swinnen
mesh_terms: D019342:Acetic Acid / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D013662:Tea; D014407:Tumor Cells, Cultured / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013662:Tea; D019014:fas Receptor; D002392:Catechin; C045651:epigallocatechin gallate; D064429:Fatty Acid Synthases; D019342:Acetic Acid