title: Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity.
abstract: The consumption of food products containing high amounts of flavonoids has been reported to lower the risk of various cancers. The mechanisms underlying the cancer-protective effects of these naturally occurring polyphenolic compounds, however, remain elusive. Based on our previous finding that the cytotoxic effect of the flavanol epigallocatechin-3-gallate on prostate cancer cells correlates with its ability to inhibit fatty acid synthase (FAS, a key lipogenic enzyme overexpressed in many human cancers), we examined the anti-lipogenic effects of a panel of 18 naturally occurring polyphenolic compounds. In addition to epigallocatechin-3-gallate, five other flavonoids, more particularly luteolin, quercetin, kaempferol, apigenin, and taxifolin, also markedly inhibited cancer cell lipogenesis. Interestingly, in both prostate and breast cancer cells, a remarkable dose-response parallelism was observed between flavonoid-induced inhibition of fatty acid synthesis, inhibition of cell growth, and induction of apoptosis. In support for a role of fatty acid synthesis in these effects, the addition of exogenous palmitate, the end product of FAS, markedly suppressed the cytotoxic effects of flavonoids. Taken together, these findings indicate that the potential of flavonoids to induce apoptosis in cancer cells is strongly associated with their FAS inhibitory properties, thereby providing a new mechanism by which polyphenolic compounds may exert their cancer-preventive and antineoplastic effects.
authors.affiliation: Laboratory for Experimental Medicine and Endocrinology, Department of Developmental Biology, Katholieke Universiteit Leuven, B-3000, Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Brusselmans
authors.forename: Ruth
authors.initials: R
authors.lastname: Vrolix
authors.forename: Guido
authors.initials: G
authors.lastname: Verhoeven
authors.forename: Johannes V
authors.initials: JV
authors.lastname: Swinnen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005347:Fibroblasts; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis; D047311:Luteolin / Q000494:pharmacology; D015394:Molecular Structure; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D019308:Palmitic Acid / Q000378:metabolism / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D059808:Polyphenols; D011794:Quercetin / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D005419:Flavonoids; D044949:Kaempferols; D008055:Lipids; D010636:Phenols; D059808:Polyphenols; D034741:RNA, Small Interfering; D019014:fas Receptor; D019308:Palmitic Acid; C006552:kaempferol; D011794:Quercetin; D064429:Fatty Acid Synthases; D047311:Luteolin