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

J Inorg Biochem. 2013 Oct:127:24-38. doi: 10.1016/j.jinorgbio.2013.05.011. Epub 2013 May 28.

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.

Keywords: Apoptosis; Cancer; Carbonimidothioate; Cell cycle; Phosphinegold(I) compounds; Thiolate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy*
  • HT29 Cells
  • Humans
  • Models, Molecular
  • Organogold Compounds / chemistry*
  • Organogold Compounds / pharmacology
  • Reference Standards

Substances

  • Antineoplastic Agents
  • Organogold Compounds