磷酸戊糖途径
葡萄糖-6-磷酸脱氢酶
化疗增敏剂
癌症研究
化学
细胞生长
酶
生物化学
药理学
脱氢酶
糖酵解
细胞毒性
生物
体外
作者
Bryan Oronsky,Jan Scicinski,Tony Reid,Arnold L. Oronsky,Corey Carter,Neil Oronsky,Pedro Cabrales
出处
期刊:PubMed
日期:2016-04-01
卷期号:21 (116): 251-65
被引量:11
摘要
The anti-proliferative effects of RRx-001, a novel RONS-mediated immuno-epigenetic and vascular normalizing anticancer agent in Phase 2 clinical trials, are not explainable via a single mechanism. Previous research suggested an association between G6PD inhibition and RRx-001 anticancer activity. The results in this study confirm and extend previous observations that RRx-001 exerts its anti-proliferative effect, at least partially, through interference with glucose 6 phosphate dehydrogenase (G6PD), a key enzyme in the pentose phosphate pathway, responsible for maintaining adequate levels of the major cellular reductant, NADPH. RRx-001 affects glucose and G6PD enzyme activity in three different cancer cell lines namely Hep G2, CACO-2, and HT-29. We observed that in all cancer cell lines tested, RRx-001 induced G6PD inhibition in a concentration dependent fashion. Inhibition of G6PD activity associated with a reduction in ribonucleotide synthesis, glutathione reduction and cell proliferation may represent an important mechanism by which RRx-001 exerts its anticancer effects.
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