Piperlongumine in combination with EGFR tyrosine kinase inhibitors for the treatment of lung cancer cells

作     者：SHAIL RAKESH MODI TERRICK ANDEY 

作者机构：Department of Pharmaceutical SciencesMassachusetts College of Pharmacy and Health SciencesWorcesterMA 01608USA 

出 版 物：《Oncology Research》 (肿瘤学研究（英文）)

年 卷 期：2024年第32卷第11期

页      面：1709-1721页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Piperlongumine(PPL) Non-small cell lung cancer(NSCLC) Tyrosine kinase inhibitors(TKI) Mutation Resistance 

摘      要：Objectives:EGFR tyrosine kinase inhibitor(EGFR-TKI)therapies such as erlotinib and gefitinib are approved for the treatment of non-small cell lung cancer(NSCLC).However,the high incidence of acquired resistance to these EGFR-TKIs may preclude their ***(PPL),an extract from the long pepper fruit(Piper longum),has been shown to possess anticancer *** purpose of the study was to investigate piperlongumine as an anticancer agent and to study a combination treatment approach with EGFR-TKIs against lung cancer ***:Anticancer efficacy of PPL,erlotinib(ERL),gefitinib(GEF),and cisplatin(CIS)were investigated in H1299 and H1975 cell *** were treated with PPL,ERL,GEF,and CIS alone,and in combination,cell viability was determined after 72 *** mechanism of PPL-induced cytotoxicity was investigated via reactive oxygen species(ROS)induction,and apoptosis induction using acridine orange/ethidium bromide staining and flow *** effect of treatment on EGFR-mediated oncogenic signaling was investigated by immunoblotting for mitogenic and apoptotic ***:PPL exhibited a potent cytotoxic effect in H1299 and H1975 cells compared to ERL,GEF,and *** treatments of PPL with GEF and ERL showed significant reductions in cancer cells compared to control in both cell lines,which were associated with apoptotic induction,but without significant ROS *** to control,PPL with GEF significantly increased apoptotic cell death in H1975as confirmed with flow *** with PPL alone and in combination induced anti-mitogenic and apoptotic responses at the molecular ***:PPL sensitized lung cancer cells to EGFR-TKI and induced potent cytotoxic effects at low concentrations.