title: The influence of R substituents in triphenylphosphinegold(I) carbonimidothioates, Ph3PAu[SC(OR)=NPh] (R=Me, Et and iPr), upon in vitro cytotoxicity against the HT-29 colon cancer cell line and upon apoptotic pathways.
abstract: The Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), compounds are significantly cytotoxic to the HT-29 cancer cell line with 1 being the most active. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis is demonstrated and both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. Compound 1 activates the p73 gene, whereas each of 2 and 3 activates the p53 gene. An additional apoptotic mechanism is exhibited by 2, that is, via the JNK/MAP pathway.
authors.affiliation: Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Chien Ing
authors.initials: CI
authors.lastname: Yeo
authors.forename: Kah Kooi
authors.initials: KK
authors.lastname: Ooi
authors.forename: Abdah Md
authors.initials: AM
authors.lastname: Akim
authors.forename: Kok Pian
authors.initials: KP
authors.lastname: Ang
authors.forename: Zainal Abidin
authors.initials: ZA
authors.lastname: Fairuz
authors.forename: Siti Nadiah Binti Abdul
authors.initials: SN
authors.lastname: Halim
authors.forename: Seik Weng
authors.initials: SW
authors.lastname: Ng
authors.forename: Hoi-Ling
authors.initials: HL
authors.lastname: Seng
authors.forename: Edward R T
authors.initials: ER
authors.lastname: Tiekink
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D019073:HT29 Cells; D006801:Humans; D008958:Models, Molecular; D050607:Organogold Compounds / Q000737:chemistry* / Q000494:pharmacology; D012015:Reference Standards
chemical_list: D000970:Antineoplastic Agents; D050607:Organogold Compounds
keywords: Apoptosis; Cancer; Carbonimidothioate; Cell cycle; Phosphinegold(I) compounds; Thiolate