title: Cytotoxicity of dioscin in human gastric carcinoma cells through death receptor and mitochondrial pathways.
abstract: In the present study, the antiproliferative effect of dioscin on human gastric carcinoma SGC-7901 cells was confirmed by 3-(4, 5-dimethylthiahiazo-zyl)-2, 5-dip-henytetrazolium bromide and flow cytometry assays. Through acridine orange-ethidium bromide double fluorescent staining, apoptotic morphology of the cells was observed. Radioimmunoassays showed that the tumor necrosis factor (TNF)-α concentration in cells treated with dioscin significantly increased compared with untreated cells. Several proteins and mRNA related to the mitochondrial and death receptor pathways were investigated. We found that the expression of Bid, bcl-2 and bcl-xl was markedly downregulated, and the expression of Bak and Bax was upregulated. In addition, cytochrome c was released from the mitochondria into the cytosol, which indicates activation of the mitrochondrial pathway by dioscin. Furthermore, upregulation of Fas, FasL (Fas ligand), TNF-α, TNF receptor-1, TNF receptor-associated factor 1 and Fas-associated protein with death domain demonstrated involvement of the death receptor pathway. Increased mRNA expression of p53 was also found in dioscin-treated SGC-7901 cells, and the activation of caspase-3 and -8 was also observed. Consequently, this study clarifies the mechanism underlying the anticancer effect of dioscin, and also indicates that dioscin may be a potential drug treatment for human gastric cancer.
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshun South Road, Dalian, 116044, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Hu
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Youwei
authors.initials: Y
authors.lastname: Xu
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
authors.forename: Xianyao
authors.initials: X
authors.lastname: Wan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494772:BAK1 protein, human; C494826:BAX protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D012333:RNA, Messenger; C495901:TP53 protein, human; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C019357:dioscin; D045304:Cytochromes c; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D004144:Diosgenin