title: A novel thiazolidine compound induces caspase-9 dependent apoptosis in cancer cells.
abstract: The forward chemogenomics strategy allowed us to identify a potent cytotoxic thiazolidine compound as an apoptosis-inducing agent. Chemical structures were designed around a thiazolidine ring, a structure already noted for its anticancer properties. Initially, we evaluated these novel compounds on liver, breast, colon and endometrial cancer cell lines. The compound 3 (ALC67) showed the strongest cytotoxic activity (IC(50) ∼5 μM). Cell cycle analysis with ALC67 on liver cells revealed SubG1/G1 arrest bearing apoptosis. Furthermore we demonstrated that cytotoxicity of this compound was due to the activation of caspase-9 involved apoptotic pathway, which is death receptor independent.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Yeditepe University, Kadıkoy, 34755 Istanbul, Turkey.
authors.forename: F Esra
authors.initials: FE
authors.lastname: Onen-Bayram
authors.forename: Irem
authors.initials: I
authors.lastname: Durmaz
authors.forename: Daniel
authors.initials: D
authors.lastname: Scherman
authors.forename: Jean
authors.initials: J
authors.lastname: Herscovici
authors.forename: Rengul
authors.initials: R
authors.lastname: Cetin-Atalay
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053453:Caspase 9 / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D053778:Thiazolidines; D053453:Caspase 9