Polychlorinated biphenyls promote cell survival through pyruvate kinase M2-dependent glycolysis in HeLa cells

Abstract

It is well known that polychlorinated biphenyls (PCBs) are typical persistent organic pollutants (POPs) in the environment. The present study investigated the effects of three PCBs including 3,3′,4,4′,5-pentachlorobiphenyl (PCB126), 2,3′,4,4′,5-pentachlorobiphenyl (PCB118), and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) on human cervical carcinoma HeLa cell survival and the possible underlying mechanisms. The results showed that PCB126, PCB118, or PCB153 exposure for 48 h significantly promoted HeLa cell survival. Meanwhile, glucose consumption, lactate production, and glycolysis-related proteins including glucose transporter-1 (GLUT1), lactate dehydrogenase (LDHA), and pyruvate dehydrogenase kinase (PDK) were remarkably elevated after three PCBs treatment, indicated PCBs stimulating glycolysis. Moreover, we found that the expression and nuclear distribution of PKM2 protein was significantly increased in PCB126, PCB118, or PCB153-treated HeLa cells. However, the enzymatic activity of PKM2 was reduced. In addition, the three congeners exposure elevated ROS levels and the expression of NADPH oxidase subunits such as NOX2, p47phox, and p40phox. The addition of antioxidant NAC antagonized the three PCBs-induced effects on PKM2, cell survival, and glycolysis. Taken together, these results indicated that PCB126, PCB118, or PCB153 exposure promotes cervical cancer HeLa cell survival by PKM2-dependent upregulation of glycolysis, which is mediated by NADPH oxidase-induced ROS production.