Lactic acidosis switches cancer cells from aerobic glycolysis back to dominant oxidative phosphorylation

// Hao Wu 1 , Minfeng Ying 1 , Xun Hu 1 1 Cancer Institute (Key Laboratory For Cancer Prevention & Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China Correspondence to: Xun Hu, email: huxun@zju.edu.cn Keywords: Warburg effect, OXPHOS, lactic acidosis Received: February 25, 2016      Accepted: May 16, 2016      Published: May 31, 2016 ABSTRACT While transformation of normal cells to cancer cells is accompanied with a switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, it is interesting to ask if cancer cells can revert from Warburg effect to OXPHOS. Our previous works suggested that cancer cells reverted to OXPHOS, when they were exposed to lactic acidosis, a common factor in tumor environment. However, the conclusion cannot be drawn unless ATP output from glycolysis and OXPHOS is quantitatively determined. Here we quantitatively measured ATP generation from glycolysis and OXPHOS in 9 randomly selected cancer cell lines. Without lactic acidosis, glycolysis and OXPHOS generated 23.7% – 52.2 % and 47.8% - 76.3% of total ATP, respectively; with lactic acidosis (20 mM lactate with pH 6.7), glycolysis and OXPHOS provided 5.7% - 13.4% and 86.6% - 94.3% of total ATP. We concluded that cancer cells under lactic acidosis reverted from Warburg effect to OXPHOS phenotype.