title: Synergistic induction of apoptosis in A549 cells by dihydroartemisinin and gemcitabine.
abstract: This report is designed to study the ability of the combined treatment with gemcitabine (Gem) and dihydroartemisinin (DHA) to induce apoptosis in a non-small-cell lung cancer cell line (A549 cells). This combination treatment synergistically inhibited cell growth by inducing apoptosis, and this synergistic action was not associated with reactive oxygen species (ROS). Although either Gem or DHA induced a significant increase in ROS generation, the combination treatment did not further enhance ROS level. Compared with single drugs, the combination treatment significantly potentiated Bak activation, loss of mitochondrial membrane potential, caspase-9 and -3 activation, indicating the important role of the Bak-mediated intrinsic apoptosis pathway in the synergistic action, which was further verified by the significant prevention of the cytotoxicity of the combination treatment by inhibiting one of caspase-9, -3 and Bcl-xL or silencing Bak. In addition, the combination treatment also synergistically activated caspase-8, and inhibition of Fas and caspase-8 presented significant prevention on the cytotoxicity of the combination treatment, indicating that the Fas-caspase-8-mediated extrinsic apoptosis pathway partially participated in the synergistic action. Collectively, the present study demonstrates a strong synergistic action of the combined treatment with Gem and DHA in inducing apoptosis of A549 cells via both the Bak-mediated intrinsic pathway and the Fas-caspase-8-mediated extrinsic pathway.
authors: MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Life Science, South China Normal University, Guangzhou, 510631, China.
authors: Chubiao
authors: C
authors: Zhao
authors: Weijie
authors: W
authors: Gao
authors: Tongsheng
authors: T
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; C494772:BAK1 protein, human; C491901:FAS protein, human; D017382:Reactive Oxygen Species; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D003841:Deoxycytidine; C039060:artenimol; D000093542:Gemcitabine