Brusselmans Koen, Vrolix Ruth, Verhoeven Guido, Swinnen Johannes V
Laboratory for Experimental Medicine and Endocrinology, Department of Developmental Biology, Katholieke Universiteit Leuven, B-3000, Leuven, Belgium.
J Biol Chem. 2005 Feb 18;280(7):5636-45. doi: 10.1074/jbc.M408177200. Epub 2004 Nov 8.
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.
据报道，食用含有大量类黄酮的食品可降低患各种癌症的风险。然而，这些天然存在的多酚化合物的防癌作用背后的机制仍不清楚。基于我们之前的发现，即黄烷醇表没食子儿茶素-3-没食子酸酯对前列腺癌细胞的细胞毒性作用与其抑制脂肪酸合酶（FAS，一种在许多人类癌症中过度表达的关键脂肪生成酶）的能力相关，我们研究了一组18种天然存在的多酚化合物的抗脂肪生成作用。除表没食子儿茶素-3-没食子酸酯外，其他五种类黄酮，特别是木犀草素、槲皮素、山奈酚、芹菜素和紫杉叶素，也显著抑制癌细胞的脂肪生成。有趣的是，在前列腺癌细胞和乳腺癌细胞中，在类黄酮诱导的脂肪酸合成抑制、细胞生长抑制和凋亡诱导之间观察到显著的剂量反应平行关系。为支持脂肪酸合成在这些作用中的作用，添加FAS的终产物外源性棕榈酸酯可显著抑制类黄酮的细胞毒性作用。综上所述，这些发现表明类黄酮诱导癌细胞凋亡的潜力与其FAS抑制特性密切相关，从而为多酚化合物发挥其防癌和抗肿瘤作用提供了一种新机制。
