title: Neferine Potentiates the Antitumor Effect of Cisplatin in Human Lung Adenocarcinoma Cells Via a Mitochondria-Mediated Apoptosis Pathway.
abstract: Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumors but its efficacy is often limited by the development of resistance and dose limiting toxicity. Neferine is an alkaloid isolated from seed embryo of Nelumbo nucifera, it has recently been shown to have anticancer effects in various human cancer cell lines. The present investigation is designed to study the chemosensitizing ability of neferine with cisplatin in A549 cells. Neferine potentiates the cisplatin induced apoptosis through the exploration of characteristic apoptotic morphological changes, induced sub-G1 cell cycle arrest, ROS hypergeneration, significant loss of cellular antioxidant enzymes, as well as loss of mitochondrial membrane potential (ΔΨM). Furthermore our results revealed that neferine combined with cisplatin down regulate the expression of Bcl-2 and up regulate the expression of Bax, Bad, Bak, release of cytochrome c, p53 levels, then activated cleavage forms of caspase-9, caspase-3, and PARP. Moreover neferine and cisplatin combination significantly down regulated the protein levels of FAK and VEGF. In addition, we observed the activity of MMP-2 and MMP-9. Thus this study provides molecular evidence for the ROS mediated apoptosis of the combinatorial regimen of cisplatin and neferine in lung cancer cells. Thus these results suggest that using neferine with cisplatin combinatorial regimen could be potentiating the effect of cisplatin and neferine reduces the cisplatin dose requirement in cancer chemotherapy. J. Cell. Biochem. 118: 2865-2876, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Translational Research Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore, Tamil Nadu, India.
authors.forename: Kalai Selvi
authors.initials: KS
authors.lastname: Sivalingam
authors.affiliation: Translational Research Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore, Tamil Nadu, India.
authors.forename: Poornima
authors.identifier: 0000-0003-3945-2402
authors.initials: P
authors.lastname: Paramasivan
authors.affiliation: Laboratory of Molecular Physiology, Department of Life Sciences, Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan.
authors.forename: Ching Feng
authors.initials: CF
authors.lastname: Weng
authors.affiliation: Translational Research Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore, Tamil Nadu, India.|Basic Medical Science, China Medical University, Taichung, Taiwan.|Departments of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Vijaya Padma
authors.identifier: 0000-0001-9154-027X
authors.initials: VP
authors.lastname: Viswanadha
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D044182:Benzylisoquinolines / Q000819:agonists / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000819:agonists / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D044182:Benzylisoquinolines; D009363:Neoplasm Proteins; C057222:neferine; D002945:Cisplatin
keywords: ANTIOXIDANTS; APOPTOSIS; CISPLATIN; LUNG CANCER; NEFERINE; ROS