Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N(iPr)CH2CH2OH] for R=Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways

• Main Authors: Jamaludin, Nazzatush Shimar, Goh, Zheng Jie, Cheah, Yoke Kqueen, Ang, Kok Pian, Sim, Jiun Horng, Khoo, Chai Hoon, Zainal Abidin, Mohd Fairuz, Abdul Halim, Siti Nadiah, Ng, Seik Weng, Seng, Hoi Ling, Tiekink, Edward Richard Tom
• Format: Article
• Published: Elsevier 2013
• Online Access: http://psasir.upm.edu.my/id/eprint/29590/; http://www.sciencedirect.com/science/article/pii/S0223523413004066

The synthesis and characterisation of R3PAu[S2CN(iPr)CH2CH2OH], for R = Ph (1), Cy (2) and Et (3)4, is reported. Compounds 1–3 are cytotoxic against the doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater potency and cytotoxicity than either of doxorubicin and cisplatin. 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 by 1, and necrosis by 2 and 3, are demonstrated, by both extrinsic and intrinsic pathways. Compound 1 activates the p53 gene, 2 activates only the p73 gene, whereas 3 activates both the p53 and p73 genes. Compounds 1 and 3 activate NF-κB, and each inhibits topoisomerase I.