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Triclosan (TCS) has been widely used as an antibacterial agent for the last several decades in personal care products. The toxicological effect of TCS has attracted more and more attention of researchers. The purpose of this study is to evaluate the cytotoxic effects of TCS in HepG2 cells and to elucidate the molecular mechanism focusing on regulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O (FoxO) pathway in the glycolytic metabolism. In this study, we evaluated the adverse effect of TCS exposure on cell viability, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity and mitochondrial membrane potential (MMP). In addition, the glycolysis process in HepG2 cells exposed to TCS was examined in terms of glucose consumption, lactate production and ATP generation. Furthermore, Affymetrix Human U133 plus 2.0 gene chips and gene function enrichment analysis were conducted to screen differential expression genes (DEGs) and potential signaling pathway. Expressions of the glycolysis-related proteins were measured and quantified with Western Blotting. The results showed that TCS could suppress the cell viability, induce oxidative stress, and cause mitochondrial damage. In addition, TCS exposure promoted the glycolysis process, as manifested by accelerated conversion of glucose to lactate and increased energy release. Western Blotting results confirmed that the expression levels of glycolysis related proteins were significantly elevated. The PI3K/Akt/FoxO pathway was identified to play a pivot role in TCS-induced glycolysis, which was further confirmed by inhibitor tests using specific inhibitors LY294002 and MK2206. In general, TCS can induce oxidative stress, cause oxidative damages and promote glycolysis in HepG2 cells, which was mediated by the PI3K/Akt/FoxO pathway. Keywords: Glycolysis, Molecular mechanism, PI3K/Akt/FoxO pathway |
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