Autophagic Activation and Decrease of Plasma MembraneCholesterol Contribute to Anticancer Activities

School of Pharmacy, National Taiwan University, No. 33,Linsen S. Rd., Zhongzheng Dist, Taipei 100, Taiwan'd97423004@ntu.edu.tw .-L.H); r00423018@gmail.com (W-J.L.)Department of Pharmacy New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital.New Taipei City 236, Taiwan6State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory DiseaseGuangzhou Institute for Respiratory Health, First Affiliated Hospital of Guangzhou Medical UniversitvGuangzhou 510370, ChinaCorrespondence: nanshan@vip.163.com (N.-S.Z.); jhguh@ntu.edu.tw (J.-HG.)

Abstract: Non-small cell lung cancer (NSCLC), an aggressive subtype of pulmonary carcinomaswith high mortality, accounts for 85% of all lung cancers. Drug resistance and high recurrencerates impede the chemotherapeutic effect, making it urgent to develop new anti-NSCLC agentsRecently, we have demonstrated that para-toluenesulfonamide is a potential anti-tumor agent inhuman castration-resistant prostate cancer (CRPC) through inhibition of Akt/mTOR/p70S6 kinasepathwav and lipid raft disruption.In the current study we further addressed the critical role ofcholesterol-enriched membrane microdomain and autophagic activation to para-toluenesulfonamideaction in killing NSCLC.Similar in CRPC,para-toluenesulfonamide inhibited the Akt/mTOR/p70S6Kpathway in NSCLC cell lines NCI-H460 and A549, leading to G1 arrest of the cell cycle and apoptosisPara-to uenesu fonamide significanf y decreased the cho estero eves of p asma membrane. xternal...