Central University of Punjab, Bathinda, Punjab, India.
Integr Cancer Ther. 2020 Jan-Dec;19:1534735420911437. doi: 10.1177/1534735420911437.
Dichloroacetate (DCA) is a metabolic modulator that inhibits pyruvate dehydrogenase activity and promotes the influx of pyruvate into the tricarboxylic acid cycle for complete oxidation of glucose. DCA stimulates oxidative phosphorylation (OXPHOS) more than glycolysis by altering the morphology of the mitochondria and supports mitochondrial apoptosis. As a consequence, DCA induces apoptosis in cancer cells and inhibits the proliferation of cancer cells. Recently, the role of miRNAs has been reported in regulating gene expression at the transcriptional level and also in reprogramming energy metabolism. In this article, we indicate that DCA treatment leads to the upregulation of let-7a expression, but DCA-induced cancer cell death is independent of let-7a. We observed that the combined effect of DCA and let-7a induces apoptosis, reduces reactive oxygen species generation and autophagy, and stimulates mitochondrial biogenesis. This was later accompanied by stimulation of OXPHOS in combined treatment and was thus involved in metabolic reprogramming of MDA-MB-231 cells.
二氯乙酸 (DCA) 是一种代谢调节剂，可抑制丙酮酸脱氢酶的活性，并促进丙酮酸流入三羧酸循环，以实现葡萄糖的完全氧化。DCA 通过改变线粒体的形态来促进氧化磷酸化 (OXPHOS)，超过糖酵解，支持线粒体凋亡。因此，DCA 诱导癌细胞凋亡并抑制癌细胞增殖。最近，miRNA 的作用已被报道可在转录水平调节基因表达，并可重新编程能量代谢。在本文中，我们指出 DCA 处理会导致 let-7a 的表达上调，但 DCA 诱导的癌细胞死亡与 let-7a 无关。我们观察到 DCA 和 let-7a 的联合作用会诱导细胞凋亡，减少活性氧生成和自噬，并刺激线粒体生物发生。这随后伴随着联合处理中 OXPHOS 的刺激，从而参与 MDA-MB-231 细胞的代谢重编程。
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