title: Dioscin-induced autophagy mitigates cell apoptosis through modulation of PI3K/Akt and ERK and JNK signaling pathways in human lung cancer cell lines.
abstract: Our previous study has revealed that dioscin, a compound with anti-inflammatory, lipid-lowering, anticancer and hepatoprotective effects, may induce autophagy in hepatoma cells. Autophagy is a lysosomal degradation pathway that is essential for cell survival and tissue homeostasis. In this study, the role of autophagy and related signaling pathways during dioscin-induced apoptosis in human lung cancer cells was investigated. Results from 4'-6-diamidino-2-phenylindole and annexin-V/PI double-staining assay showed that caspase-3- and caspase-8-dependent, and dose-dependent apoptoses were detected after a 24-h dioscin treatment. Meanwhile, autophagy was detected as early as 12 h after an exposure to low-dose dioscin, as indicated by an up-regulated expression of LC3-II and beclin-1 proteins. Blockade of autophagy with bafilomycin A1 or 3-methyladenine sensitized the A549 and H1299 cells to apoptosis. Treatment of A549 and H1299 cells with dioscin caused a dose-dependent increase in ERK1/2 and JNK1/2 activity, accompanied with a decreased PI3K expression and decreased phosphorylation of Akt and mTOR. Taken together, this study demonstrated for the first time that autophagy occurred earlier than apoptosis during dioscin-induced human lung cancer cell line apoptosis. Dioscin-induced autophagy via ERK1/2 and JNK1/2 pathways may provide a protective mechanism for cell survival against dioscin-induced apoptosis to act as a cytoprotective reaction.
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, 110, Section 1 Chien-Kuo N. Road, Taichung, 402, Taiwan, ROC.
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, 402, Taiwan, ROC.|Department of Pathology & Laboratory Medicine, MacKay Memorial Hospital Hsinchu Branch, Hsinchu, 690, Taiwan, ROC.
authors.forename: Te-Lung
authors.initials: TL
authors.lastname: Tsai
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, 402, Taiwan, ROC.|Department of Biochemistry, Chung Shan Medical University, Taichung, 402, Taiwan, ROC.
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, 402, Taiwan, ROC. wcj@csmu.edu.tw.|Department of Medical Research, Chung Shan Medical University Hospital, Taichung, 402, Taiwan, ROC. wcj@csmu.edu.tw.
authors.forename: Chau-Jong
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, 110, Section 1 Chien-Kuo N. Road, Taichung, 402, Taiwan, ROC. hlchiou@csmu.edu.tw.|Department of Clinical Laboratory, Chung Shan Medical University, Taichung, 402, Taiwan, ROC. hlchiou@csmu.edu.tw.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Chiou
mesh_terms: D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D006801:Humans; D007211:Indoles; D008175:Lung Neoplasms / Q000473:pathology*; D048670:MAP Kinase Kinase 4 / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051058:Oncogene Protein v-akt / Q000502:physiology*; D015388:Organelles / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D017304:Annexin A5; D005456:Fluorescent Dyes; D007211:Indoles; C019357:dioscin; C007293:DAPI; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D048670:MAP Kinase Kinase 4; D004144:Diosgenin
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