title: The synergistic effect of resveratrol in combination with cisplatin on apoptosis via modulating autophagy in A549 cells.
abstract: Several studies have shown that combination treatment with natural products and chemotherapy agents can improve the sensitivity and cytotoxicity of chemotherapy agents. Resveratrol, a natural product, has many biological effects including antitumor and antiviral activities, as well as vascular protective effect. The aim of this study is to investigate the synergistic anticancer effect of resveratrol in combination with cisplatin and the potential anticancer mechanisms involved in A549 cells. The results obtained from Cell Counting Kit-8 and isobolographic analysis demonstrated that combination of resveratrol and cisplatin resulted in synergistic cytotoxic effects in A549 cells. Results from Hoechst staining, flow cytometry and western blot analysis suggested that resveratrol enhanced cisplatin-mediated apoptosis. Meanwhile, the changes of LC3-II and P62 levels and formation of autophagosome suggested that resveratrol in combination with cisplatin triggered autophagy. More importantly, inhibiting autophagy by 3-methyladenine markedly attenuated the apoptosis caused by combination of resveratrol and cisplatin in A549 cells. Taken together, our study provides the first evidence that resveratrol combined with cisplatin synergistically induce apoptosis via modulating autophagic cell death in A549 cells. These findings also help us to understand the role of natural products in combination with chemotherapy agents in lung cancer.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Song
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China wpxie@njmu.edu.cn.
authors.forename: Weiping
authors.initials: W
authors.lastname: Xie
mesh_terms: D000072283:A549 Cells; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D000071182:Autophagosomes / Q000187:drug effects / Q000473:pathology; D001343:Autophagy / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage*; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C118585:P62 protein, human; D016601:RNA-Binding Proteins; D013267:Stilbenes; C025946:3-methyladenine; D051057:Proto-Oncogene Proteins c-akt; D000225:Adenine; D002945:Cisplatin; D000077185:Resveratrol
keywords: apoptosis; autophagy; cisplatin; non-small cell lung cancer; resveratrol