title: G2/M cell cycle arrest on HT-29 cancer cells and toxicity assessment of triphenylphosphanegold(I) carbonimidothioates, Ph3PAu[SC(OR)=NPh], R=Me, Et, and iPr, during zebrafish development.
abstract: Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death. Cell cycle analysis showed the majority of treated HT-29 cells were arrested at the G2/M checkpoint after 24h; results of both assays were confirmed by changes in populations of relevant genes (PCR array analysis). Cell invasion studies showed inhibition of metastasis through Matrigel™ matrix to 17-22% cf. untreated cells. LC50values were determined in zebrafish (8.36, 8.17, and 7.64μM for 1-3). Finally, the zebrafish tolerated doses of 1 and 2 up to 0.625μM, and 3 was tolerated at even higher doses of up to 1.25μM.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; Research Centre for Crystalline Materials, Faculty of Science and Technology, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.
authors.forename: Kah Kooi
authors.initials: KK
authors.lastname: Ooi
authors.affiliation: Research Centre for Crystalline Materials, Faculty of Science and Technology, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.
authors.forename: Chien Ing
authors.initials: CI
authors.lastname: Yeo
authors.affiliation: Department of Biotechnology, Faculty of Engineering and Science, Malaysia University of Science and Technology, 47301 Petaling Jaya, Selangor, Malaysia.
authors.forename: Theventhiran
authors.initials: T
authors.lastname: Mahandaran
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
authors.forename: Kok Pian
authors.initials: KP
authors.lastname: Ang
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
authors.forename: Abdah Md
authors.initials: AM
authors.lastname: Akim
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
authors.forename: Yoke-Kqueen
authors.initials: YK
authors.lastname: Cheah
authors.affiliation: Department of Biological Sciences, Faculty of Science and Technology, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: hoilings@sunway.edu.my.
authors.forename: Hoi-Ling
authors.initials: HL
authors.lastname: Seng
authors.affiliation: Research Centre for Crystalline Materials, Faculty of Science and Technology, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: edwardt@sunway.edu.my.
authors.forename: Edward R T
authors.initials: ERT
authors.lastname: Tiekink
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D050607:Organogold Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology*
chemical_list: D003603:Cytotoxins; D050607:Organogold Compounds
keywords: Apoptosis; Carbonimidothioates; Gold(I) compounds; HT-29 cancer cell; Phosphanegold(I) thiolates; Zebrafish