title: A novel selenadiazole derivative induces apoptosis in human glioma cells by dephosphorylation of AKT.
abstract: Selenadiazole derivatives are synthetic organoselenium compounds with improved anticancer activity and greater selectivity than inorganic selenium. In this study, 4-(benzo[c][1,2,5]selenadiazol-6-yl)-benzene-1,2-diamine (BSBD) was shown to induce time- and dose-dependent apoptosis in SWO-38 human glioma cells by accumulation of a sub-G1 cell population, DNA fragmentation, nuclear condensation, caspase activation and poly(ADP-ribose) polymerase (PARP) cleavage. Further mechanistic investigation showed that BSBD treatment induced dephosphorylation of AKT and DNA damage-mediated activation of p53, leading to extensive apoptosis through the mitochondrial pathway. Our findings suggest that BSBD represents a potential human glioma therapeutic.
authors.affiliation: Guangdong Province Key Laboratory of Molecule Immunology and Antibody Engineering, Department of Pathology, Jinan University.
authors.forename: Yikai
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shanyuan
authors.initials: S
authors.lastname: Zheng
authors.forename: Sai-Ming
authors.initials: SM
authors.lastname: Ngai
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
authors.forename: Jinying
authors.initials: J
authors.lastname: Li
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
authors.forename: Xueyun
authors.initials: X
authors.lastname: Zhong
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D003959:Diamines / Q000737:chemistry* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016566:Organoselenium Compounds / Q000737:chemistry* / Q000633:toxicity; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C000598355:4-(benzo(c)(1,2,5)selenadiazol-6-yl)-benzene-1,2-diamine; D000970:Antineoplastic Agents; D003959:Diamines; D016566:Organoselenium Compounds; D016159:Tumor Suppressor Protein p53; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases