Epigallocatechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells
Epigallocatechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells
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DOI：
10.1002/ijc.11317
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发表时间：
2003-10-10
影响因子：
6.4
通讯作者：
Swinnen, JV
中科院分区：
文献类型：
--
作者：
Brusselmans, K;De Schrijver, E;Swinnen, JV
脂肪酸合成酶（FAS）化学抑制剂在体外和体内异种肿瘤移植中抑制几种癌细胞系的生长和诱导凋亡。最近，绿茶成分表没食子儿茶素-3-没食子酸酯（EGCG）被证明是鸡肝提取物中FAS的天然抑制剂。本研究探讨了EGCG是否抑制体外培养前列腺癌细胞FAS活性，以及这种抑制作用如何影响内源性脂质合成、细胞增殖和细胞活力。EGCG剂量依赖性地抑制LNCaP细胞中FAS的高水平活性，这种抑制与内源性脂质合成减少、细胞生长抑制和诱导凋亡并行。相比之下，表儿茶素（EC），另一种密切相关的绿茶多酚化合物，不抑制FAS，对LNCaP细胞的生长和活力没有影响。用EGCG治疗FAS活性低的非恶性细胞（成纤维细胞）导致生长速度下降，但不诱导凋亡。这些数据表明，EGCG与目前已知的合成抑制剂一样有效地抑制FAS活性，并选择性地导致LNCaP细胞的凋亡，而非肿瘤成纤维细胞的凋亡。这些发现证实了EGCG在完整细胞中是一种有效的FAS天然抑制剂，并加强了EGCG作为化学预防和治疗抗肿瘤药物的分子基础。(C) 2003 Wiley-Liss, Inc。
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. (C) 2003 Wiley-Liss, Inc.