Oroxylin A inhibits glycolysis-dependent proliferation of human breast cancer via promoting SIRT3-mediated SOD2 transcription and HIF1 alpha destabilization
Oroxylin A inhibits glycolysis-dependent proliferation of human breast cancer via promoting SIRT3-mediated SOD2 transcription and HIF1 alpha destabilization
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Oroxylin A 通过促进 SIRT3 介导的 SOD2 转录和 HIF1 α 不稳定来抑制人乳腺癌的糖酵解依赖性增殖
DOI：
10.1038/cddis.2015.86
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发表时间：
2015
影响因子：
9
通讯作者：
Lu N.
中科院分区：
文献类型：
--
作者：
Wei L.;Zhou Y.;Qiao C.;Ni T.;Li Z.;You Q.;Guo Q.;Lu N.
细胞代谢的改变在癌症的发生和发展中起着核心作用。Oroxylin A是一种中药中的活性黄酮类化合物，以前被证明可以调节癌细胞的糖酵解。然而，Oroxylin A调节糖酵解的机制仍不是很清楚。在这里，我们表明，奥罗西林A通过Sirtuin3(Sirt3)介导的低氧诱导因子1α失稳(HIF1α)来抑制乳腺癌细胞的糖酵解，它控制糖酵解基因的表达。Oroxylin A通过SIRT3调节FOXO3a的DNA结合活性促进超氧化物歧化酶(SOD2)基因的表达，并通过促进SIRT3介导的脱乙酰基增加SOD2的活性。在体内，Oroxylin A抑制与糖酵解抑制相关的移植的人乳腺肿瘤的生长。这些数据表明，Oroxylin A通过激活sirt3抑制HIF1α的稳定，从而抑制依赖糖酵解的乳腺癌细胞的增殖，为sirt3刺激的癌症治疗提供了临床前信息。
Alterations of cellular metabolism play a central role in the development and progression of cancer. Oroxylin A, an active flavonoid of a Chinese traditional medicinal plant, was previously shown to modulate glycolysis in cancer cells. However, the mechanism by which oroxylin A regulates glycolysis is still not well defined. Here, we show that oroxylin A inhibits glycolysis in breast cancer cells via the Sirtuin 3 (SIRT3)-mediated destabilization of hypoxia-inducible factor 1α (HIF1α), which controls glycolytic gene expression. Oroxylin A promotes superoxide dismutase (SOD2) gene expression through SIRT3-regulated DNA-binding activity of FOXO3a and increases the activity of SOD2 by promoting SIRT3-mediated deacetylation. In vivo, oroxylin A inhibits the growth of transplanted human breast tumors associated with glycolytic suppression. These data indicate that oroxylin A inhibits glycolysis-dependent proliferation of breast cancer cells, through the suppression of HIF1α stabilization via SIRT3 activation, providing preclinical information for the cancer therapies of SIRT3 stimulation.