title: Artemisinin induces caspase-8/9-mediated and Bax/Bak-independent apoptosis in human lung adenocarcinoma (ASTC-a-1) cells.
abstract: Artemisinin (ARTE), an antimalarial phytochemical component from the sweet wormwood plant, has been shown a potential anticancer activity by inducing cell apoptosis. The aim of this report is to explore the mechanism of ARTE-induced human lung adenocarcinoma (ASTC-a-1) cell apoptosis. Cell counting kit (CCK-8) assay showed that ARTE induced cytotoxcity in a dose- and time-dependent manner. Confocal microscopy fluorescence imaging of cells stained with Hoechst 33258 and flow cytometry (FCM) analysis of cells stained with Annexin V-FITC/propidium iodide (PI) showed that ARTE induced reactive oxygen species (ROS)-dependent apoptosis. Confocal fluorescence resonance energy transfer (FRET) imaging of single living cells expressing SCAT3, SCAT9 or CFP-Bid-YFP and fluorometic substrate assay showed that ARTE induced the activation of caspase-3, -8 and -9. Moreover, inhibition of caspase-8 or -9 completely blocked ARTE-induced apoptosis which was only partially attenuated by caspase-3 inhibitor. Interestingly, silencing Bax and Bak by RNA interference (RNAi) did not attenuate ARTE-induced apoptosis. Collectively, ARTE induces caspase-dependent but Bax/Bak-independent apoptosis in ASTC-a-1 cells.
authors.affiliation: College of Life Science, South China Normal University, Guangzhou, China MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, South China Normal University, Guangzhou, China.
authors.forename: Feng-Lian
authors.initials: FL
authors.lastname: Xiao
authors.affiliation: MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, South China Normal University, Guangzhou, China.
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Gao
authors.affiliation: Laboratory of Laser Sports Medicine, South China Normal University, Guangzhou, China.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, South China Normal University, Guangzhou, China.
authors.forename: Tong-Sheng
authors.initials: TS
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D053181:Caspase 8 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D045744:Cell Line, Tumor; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D018613:Microscopy, Confocal; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; C494826:BAX protein, human; D051028:bcl-2-Associated X Protein; C031327:artemisinin; D053181:Caspase 8; D053453:Caspase 9
keywords: Artemisinin (ARTE); Bax/Bak; apoptosis; caspase; fluorescence resonance energy transfer (FRET)