Aim To investigate the apoptosis of lung cancer cells A549 induced by quercetin and the regulation of survivin and Bcl-2 on A549 cells induced by quercetin.Methods MTT,fluorescence stain,flow cytometric analysis and immunocytochemistry stain were carried out.Results Quercetin had a significant inhibition on growth and proliferation of A549 cell in a concentration-and time-dependent manner.Evidence was provided that apoptosis occurred in A549 cells treated with quercetin using fluorescence microscopy.Quercetin arrested A549 cells at the G0/G1 phase by FCM analyses.Expression of survivin and Bcl-2 protein were decreased,and activity of caspase-3 were enhanced.Conclusion Quercetin could induce apoptosis of A549 cells.The arrested cell cycle and the down-regulation of survivin and Bcl-2 protein could activate caspase-3 resulting in cells apoptosis,which may contribute to the apoptosis mechanisms.The down-regulated survivin and Bcl-2 may play an important role in A549 cells apoptosis induced by quercetin.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.