Genistein downregulates de novo lipid synthesis and impairs cell proliferation in human lung cancer cells
Genistein downregulates de novo lipid synthesis and impairs cell proliferation in human lung cancer cells
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DOI：
10.1258/ebm.2011.010265
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发表时间：
2011-06-01
影响因子：
3.2
通讯作者：
Igal, R. Ariel
中科院分区：
文献类型：
--
作者：
Hess, Daniel;Igal, R. Ariel
癌细胞需要高水平的脂质合成来产生结构、信号和能量脂质以支持连续复制。我们和其他人已经报道，组成性增加的脂肪生成，主要是通过串联激活乙酰辅酶A羧化酶，脂肪酸合成酶和硬脂酰辅酶A去饱和酶-1（SCD 1），是维持癌细胞的生物学特征的关键，使这种代谢途径成为营养和药理学干预的潜在抗癌靶点。异黄酮是生物学上有效的植物化合物，具有明确的抗脂肪生成和抗癌特性;然而，这些营养药物对癌细胞中脂质生物合成的调节作用仍不清楚。在这里，我们表明，染料木素，丰富的大豆中，降低了SCD 1蛋白在H460人肺腺癌细胞的水平，从而降低了油酸的生物合成速率，以及其存在于癌细胞脂质。此外，染料木黄酮促进了主要磷脂、三酰甘油和胆固醇酯的从头合成的显著减少。最后，用染料木黄酮处理的癌细胞显示出细胞增殖的显著减少，这是由于阻断了细胞周期通过G（2）/M期的进展。作为一个整体，我们的数据表明，通过全面下调脂质生物合成，染料木黄酮抑制癌细胞生长，强调这种植物化合物作为一种潜在的治疗剂对肺癌，一种疾病的治疗选择仍然有限的相关性。
Cancer cells require high levels of lipid synthesis to produce structural, signaling and energetic lipids to support continuous replication. We and others have reported that constitutively increased lipogenesis, mainly by the tandem activation of acetylCoA carboxylase, fatty acid synthase and stearoyl-CoA desaturase-1 (SCD1), is critical to sustain the biological features of cancer cells, making this metabolic pathway a potential anticancer target for nutritional and pharmacological interventions. Isoflavones are biologically potent botanical compounds that possess clear antilipogenic and anticancer properties; however, the regulatory effects of these nutraceutical agents on lipid biosynthesis in cancer cells are still not well understood. Here we show that genistein, an isoflavone abundant in soybeans, decreased the levels of SCD1 protein in H460 human lung adenocarcinoma cells, consequently reducing the rate of biosynthesis of oleic acid as well as its presence in cancer cell lipids. Moreover, genistein promoted a marked reduction in de novo synthesis of major phospholipids, triacylglycerol and cholesterolesters. Finally, cancer cells treated with genistein displayed a dramatic reduction in cell proliferation as a result of a blockade in cell cycle progression through G(2)/M phases. As a whole, our data suggest that, by globally downregulating lipid biosynthesis, genistein suppresses cancer cell growth, emphasizing the relevance of this botanical compound as a potential therapeutic agent against lung cancer, a disease for which therapeutic choices remain limited.