Epigallocatechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells.
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.
Brusselmans
Koen
K
Laboratory for Experimental Medicine and Endocrinology, Department of Developmental Biology, Gasthuisberg, Catholic University of Leuven, Leuven, Belgium.
De Schrijver
Ellen
E
Heyns
Walter
W
Verhoeven
Guido
G
Swinnen
Johannes V
JV
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
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013662:Tea; D019014:fas Receptor; D002392:Catechin; C045651:epigallocatechin gallate; D064429:Fatty Acid Synthases; D019342:Acetic Acid