Brusselmans Koen, De Schrijver Ellen, Heyns Walter, Verhoeven Guido, Swinnen Johannes V
Laboratory for Experimental Medicine and Endocrinology, Department of Developmental Biology, Gasthuisberg, Catholic University of Leuven, Leuven, Belgium.
Int J Cancer. 2003 Oct 10;106(6):856-62. 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.
脂肪酸合酶（FAS）的化学抑制剂在体外的几种癌细胞系以及体内的肿瘤异种移植模型中可抑制生长并诱导细胞凋亡。最近，绿茶成分表没食子儿茶素-3-没食子酸酯（EGCG）在鸡肝提取物中被证明可作为FAS的天然抑制剂。在此，我们研究了EGCG是否能抑制培养的前列腺癌细胞中的FAS活性，以及这种抑制如何影响内源性脂质合成、细胞增殖和细胞活力。EGCG可剂量依赖性地抑制LNCaP细胞中高水平的FAS活性，这种抑制伴随着内源性脂质合成减少、细胞生长受抑制以及细胞凋亡的诱导。相比之下，另一种密切相关的绿茶多酚化合物表儿茶素（EC）不抑制FAS，对LNCaP细胞生长或活力没有影响。用EGCG处理FAS活性较低的非恶性细胞（成纤维细胞）会导致生长速率下降，但不会诱导细胞凋亡。这些数据表明，EGCG抑制FAS活性的效率与目前已知的合成抑制剂相当，并且能选择性地诱导LNCaP细胞凋亡，而非肿瘤性成纤维细胞。这些发现确立了EGCG作为完整细胞中FAS的有效天然抑制剂的地位，并加强了将EGCG用作化学预防和治疗抗肿瘤药物的分子基础。
