stilbenes and Adenocarcinoma--Bronchiolo-Alveolar

Iridium(III) complexes have attracted more and more attention in the past few years because of their potential antineoplastic activity. In this study, four Ir

Topics: A549 Cells; Adenocarcinoma, Bronchiolo-Alveolar; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line; Cell Survival; Coordination Complexes; Humans; Iridium; Lung Neoplasms; Models, Chemical; Molecular Structure; Reactive Oxygen Species; Spectrophotometry; Stilbenes

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.

Topics: A549 Cells; Adenine; Adenocarcinoma, Bronchiolo-Alveolar; Apoptosis; Autophagosomes; Autophagy; Cisplatin; Drug Synergism; Humans; Lung Neoplasms; Microscopy, Electron, Transmission; Microtubule-Associated Proteins; Neoplasm Proteins; Proto-Oncogene Proteins c-akt; Resveratrol; RNA-Binding Proteins; Stilbenes