Genistein downregulates de novo lipid synthesis and impairs cell proliferation in human lung cancer cells

Abstract

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 acetyl-CoA 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 G₂/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.