期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 89, 期 -, 页码 263-273出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2015.08.006
关键词
Dichloroacetate (DCA); Fractionated/split-dose; Non-small cell lung cancer (NSCLC); Double strand DNA break repair; Warburg effect
资金
- Departments of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN
- Medical Sciences (Indiana University, Bloomington)
- Susan B. Komen for the Cure [KG081561]
We investigated whether altering Warburg metabolism (aerobic glycolysis) by treatment with the metabolic agent dichloroacetate (DCA) could increase the X-ray-induced cell killing of the radiation-resistant human non-small-cell lung cancer (NSCLC) cell lines A549 and H1299. Treatment with 50 mM DCA decreased lactate production and glucose consumption in both A549 and H1299, clear indications of attenuated aerobic glycolysis. In addition, we found that DCA treatment also slowed cell growth, increased population doubling time, and altered cell cycle distribution. Furthermore, we report that treatment with 50 mM DCA significantly increased single and fractionated X-ray-induced cell killing of A549 and H1299 cells. Assay of DNA double strand break repair by neutral comet assays demonstrated that DCA inhibited both the fast and the slow kinetics of X-ray-induced DSB repair in both A549 and H1299 NSCL cancer cells. Taken together the data suggest a correlation between an attenuated aerobic glycolysis and enhanced cytotoxicity and radiation induced cell killing in radiation resistant NSCLC cells. (C) 2015 Elsevier Inc. All rights reserved.
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