2,3'4,4',5-Pentachlorobiphenyl induces hepatocellular carcinoma cell proliferation through pyruvate kinase M2-dependent glycolysis.

2,3'4,4',5-Pentachlorobiphenyl induces hepatocellular carcinoma cell proliferation through pyruvate kinase M2-dependent glycolysis. Toxicol Lett. 2019 Jun 25;: Authors: Liang W, Zhang Y, Song L, Li Z Abstract Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs) and are associated with the progression of many cancers, including liver cancer. The present study investigated the effect of 2,3'4,4',5-pentachlorobiphenyl (PCB118) on hepatocellular carcinoma cell proliferation and its underlying mechanisms. The results indicated that PCB118 exposure promotes the proliferation and glycolysis of hepatocellular carcinoma SMMC-7721 cells. Moreover, PCB118 exposure increased the expression level of pyruvate kinase M2 (PKM2) and its nuclear translocation, whereas treatment with PKM2 shRNA suppressed the induction of cell proliferation and glycolysis by PCB118. PCB118 stimulated reactive oxygen species (ROS) production by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Treatment with the antioxidants N-acetyl-L-cysteine (NAC) and superoxide dismutase (SOD) prevented PCB118-induced effects on PKM2, cell proliferation and glycolysis. Furthermore, we found that PCB118 activated NADPH oxidase through the aryl hydrocarbon receptor (AhR) in SMMC-7721 cells. Consistently, treatment with AhR shRNA suppressed PCB118-induced effects on PKM2, cell proliferation and glycolysis. Overall, these results indica...
Source: Toxicology Letters - Category: Toxicology Authors: Tags: Toxicol Lett Source Type: research