Quinocetone (QCT, 3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide) is widely used as a veterinary drug and animal feed additive in China. Although it promotes growth and improves feed efficiency, QCT's in vitro and in vivo toxicities remain uncertain. This study was conducted to explore the mechanism of QCT-induced autophagy in HepG2 cells. By the results obtained from monodansylcadaverine (MDC) staining, ultrastructural observation by transmission electron microscopy (TEM), as well as Western blotting analysis for LC3, p62, and Beclin-1, it was demonstrated that QCT induced autophagy in HepG2 cells. Furthermore, PI3K/AKT inhibitor significantly enhanced QCT-induced autophagy, while TSC2 knockdown attenuated this process. In addition, inhibition of autophagy by pharmacological approach remarkably increased the viability of QCT-treated cells detected by MTT assay, suggesting that QCT-triggered autophagy may play as a promotion mechanism for cell death. Meanwhile, apoptosis was markedly downregulated after autophagy blockage, and evaluated by flow cytometry and Western blotting analysis for caspase-3 cleavage. Consequently, these results suggested that QCT-induced autophagy was mediated by AKT/TSC2/p70S6K signaling pathway, and inhibition of autophagy promoted QCT-treated cell survival by attenuating apoptosis.
Anti-Bacterial Agents Apoptosis