title: Neferine augments therapeutic efficacy of cisplatin through ROS- mediated non-canonical autophagy in human lung adenocarcinoma (A549 cells).
abstract: Combination of dietary components with chemotherapy drugs is an emerging new strategy for cancer therapy to increase antitumor responses. Neferine, major bisbenzylisoquinoline alkaloid isolated from the seed embryo of Nelumbo nucifera (Lotus). In the present study, we investigated the efficacy of the combinatorial regimen of neferine and cisplatin compared to cisplatin high dose in human lung adenocarcinoma (A549) cells. Co-treatment with neferine enhanced cisplatin-induced autophagy in A549 cells was accompanied by Acidic vesicular accumulation (AVO), enhanced generation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH), down regulation of PI3K/AKT/mTOR pathway, conversion of LC3B-I to LC3B-II. This enhanced autophagy developed via a non-canonical mechanism that did not require Beclin-1, PI3KCIII. In conclusion, these results suggest that neferine enhances cisplatin -induced autophagic cancer cell death through downregulation of PI3K/Akt/mTOR signaling pro-survival pathway and ROS- mediated Beclin-1 and PI3K CIII independent autophagy in human lung adenocarcinoma (A549 cells).
authors.affiliation: Translational Research Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore, Tamil Nadu, India.
authors.forename: Sivalingam
authors.initials: S
authors.lastname: Kalai Selvi
authors.affiliation: Molecular Genetics and Breeding Laboratory, Directorate of Poultry Research, Rajendranagar, Hyderabad, Telangana, India.
authors.forename: Amirthalingam
authors.initials: A
authors.lastname: Vinoth
authors.affiliation: Laboratory of Molecular Physiology, Institute of Biotechnology, Department of Life Sciences, National Dong Hwa University, Hualien 974, Taiwan.
authors.forename: Thiyagarajan
authors.initials: T
authors.lastname: Varadharajan
authors.affiliation: Laboratory of Molecular Physiology, Institute of Biotechnology, Department of Life Sciences, National Dong Hwa University, Hualien 974, Taiwan. Electronic address: cfweng@mail.ndhu.edu.tw.
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. Electronic address: vvijayapadma@rediffmail.com.
authors.forename: Viswanadha
authors.initials: V
authors.lastname: Vijaya Padma
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000378:metabolism; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000071186:Beclin-1; D044182:Benzylisoquinolines; D002945:Cisplatin; D005978:Glutathione; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D058570:TOR Serine-Threonine Kinases; C057222:neferine; C546842:MTOR protein, human
keywords: Autophagy; Cisplatin; Human lung adenocarcinoma (A549) cells; Neferine; ROS