title: Anti-cancer effects of dioscin on three kinds of human lung cancer cell lines through inducing DNA damage and activating mitochondrial signal pathway.
abstract: Dioscin, a natural steroid saponin, has been widely investigated. However, its anti-cancer activities on human lung cancer cells are still unknown. In the present paper, the inhibitory effects of dioscin were investigated, and the results showed that dioscin inhibited the proliferation of human A549, NCI-H446 and NCI-H460 cancer cells. DNA damage and cell apoptosis in dioscin-treated cells were found through single cell gel electrophoresis and in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. Furthermore, dioscin caused mitochondrial structure changes and blocked cell cycle at S phase based on transmission electron microscope and flow cytometry analysis. In addition, dioscin treatment caused the release of cytochrome c from mitochondria into cytosol. The activities of Caspase-3 and -9 in dioscin-treated groups were significantly increased compared with control group. Western blotting analysis showed that dioscin significantly down-regulated the expressions of Bcl-2 and Bcl-xl, and up-regulated the expressions of Bax, Bak and Bid. Our results indicate that dioscin has anticancer activities against human lung cancer cells through inducing cell cycle arrest, DNA damage and activating mitochondrial signal pathway.
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian 116044, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Wei
authors.forename: Yousong
authors.initials: Y
authors.lastname: Xu
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.forename: Youwei
authors.initials: Y
authors.lastname: Xu
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.forename: Huijun
authors.initials: H
authors.lastname: Sun
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000648:ultrastructure; D000077192:Adenocarcinoma of Lung; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000378:metabolism / Q000648:ultrastructure; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004249:DNA Damage; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D021381:Protein Transport / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C019357:dioscin; D004144:Diosgenin
keywords: Anti-cancer; DNA damage; Dioscin; Human lung cancer cell lines; Mitochondrial pathway