Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome, Italy.
Cancer Res. 2012 Sep 1;72(17):4526-36. doi: 10.1158/0008-5472.CAN-12-1741. Epub 2012 Jul 6.
Anticancer drug efficacy might be leveraged by strategies to target certain biochemical adaptations of tumors. Here we show how depriving cancer cells of glutamine can enhance the anticancer properties of 3-bromopyruvate, a halogenated analog of pyruvic acid. Glutamine deprival potentiated 3-bromopyruvate chemotherapy by increasing the stability of the monocarboxylate transporter-1, an effect that sensitized cells to metabolic oxidative stress and autophagic cell death. We further elucidated mechanisms through which resistance to chemopotentiation by glutamine deprival could be circumvented. Overall, our findings offer a preclinical proof-of-concept for how to employ 3-bromopyruvate or other monocarboxylic-based drugs to sensitize tumors to chemotherapy.
通过针对肿瘤某些生化适应性的策略，可以利用抗癌药物的疗效。在这里，我们展示了剥夺癌细胞谷氨酰胺如何增强 3-溴丙酮酸（丙酮酸的卤代类似物）的抗癌特性。谷氨酰胺剥夺通过增加单羧酸转运蛋白-1 的稳定性来增强 3-溴丙酮酸化疗的效果，这一作用使细胞对代谢氧化应激和自噬性细胞死亡敏感。我们进一步阐明了通过谷氨酰胺剥夺来抵抗化学增敏的机制。总的来说，我们的研究结果为如何利用 3-溴丙酮酸或其他基于单羧酸的药物使肿瘤对化疗敏感提供了临床前的概念验证。
