Epigallocatechin‐3‐gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells

• Published in: International journal of cancer Vol. 106; no. 6; pp. 856 - 862
• Main Authors: Brusselmans, Koen, De Schrijver, Ellen, Heyns, Walter, Verhoeven, Guido, Swinnen, Johannes V.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 10-10-2003; Wiley-Liss
• Subjects: Acetic Acid - metabolism; Antineoplastic agents; Antineoplastic Agents - pharmacology; apoptosis; Apoptosis - drug effects; Biological and medical sciences; Catechin - analogs & derivatives; Catechin - pharmacology; Cell Division - drug effects; EGCG; Enzyme Inhibitors - pharmacology; Epithelial Cells - metabolism; Epithelial Cells - pathology; fas Receptor - metabolism; fatty acid synthase; Fatty Acid Synthases - antagonists & inhibitors; Fibroblasts - drug effects; Fibroblasts - metabolism; General aspects; Humans; Male; Medical sciences; Pharmacology. Drug treatments; prostate cancer; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - pathology; Tea; Tumor Cells, Cultured - drug effects; Antineoplastic agent; Human; Acyltransferases; Catechin; Urinary system disease; Carcinoma; Prostate disease; Enzyme; Transferases; Enzyme inhibitor; Malignant tumor; In vitro; Biological activity; Fatty-acid synthase; Polyphenol; Cell death; Analog; Established cell line; Lipogenesis; Male genital diseases; Prostate; Apoptosis
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.11317

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. © 2003 Wiley‐Liss, Inc.