Autophagic Activation and Decrease of Plasma Membrane Cholesterol Contribute to Anticancer Activities in Non-Small Cell Lung Cancer
Autophagic Activation and Decrease of Plasma Membrane Cholesterol Contribute to Anticancer Activities in Non-Small Cell Lung Cancer
Blog Article
Non-small cell lung cancer (NSCLC), an aggressive subtype of pulmonary carcinomas with high mortality, accounts for 85% of all lung cancers.Drug resistance and high recurrence rates impede the chemotherapeutic effect, making it urgent to develop new anti-NSCLC agents.Recently, we have demonstrated that para-toluenesulfonamide is a potential anti-tumor agent in human castration-resistant prostate cancer (CRPC) through inhibition of Akt/mTOR/p70S6 kinase pathway and lipid raft disruption.In the current study, we further addressed the critical role of cholesterol-enriched membrane microdomain and autophagic activation to para-toluenesulfonamide action in killing NSCLC.Similar in CRPC, para-toluenesulfonamide inhibited the Akt/mTOR/p70S6K pathway in NSCLC cell lines NCI-H460 and A549, leading to click here G1 arrest of the cell cycle and apoptosis.
Para-toluenesulfonamide significantly decreased the cholesterol levels of plasma membrane.External cholesterol supplement rescued para-toluenesulfonamide-mediated effects.Para-toluenesulfonamide induced a profound increase of LC3-II protein expression and a significant decrease of p62 expression.Double staining of lysosomes and cellular cholesterol showed para-toluenesulfonamide-induced lysosomal transportation of cholesterol, which was validated using flow cytometric analysis of lysosome staining.Moreover, autophagy inhibitors could blunt para-toluenesulfonamide-induced effect, indicating autophagy induction.
In conclusion, the data suggest click here that para-toluenesulfonamide is an effective anticancer agent against NSCLC through G1 checkpoint arrest and apoptotic cell death.The disturbance of membrane cholesterol levels and autophagic activation may play a crucial role to para-toluenesulfonamide action.