In vivo studies of highly cytotoxic gold(I)-phosphine dithiocarbamate complexes: Induction of ROS-mediated endoplasmic reticulum stress

Gold phosphine complexes, namely auranofin, are being used in the clinic as anti-rheumatoid arthritis agents for almost a decade. Because of its potent ability to generate reactive oxygen species (ROS), we postulated that it could be possible to harness it to upset and disrupt cellular redox balance as a therapeutic strategy against cancer. We prepared novel Au(I)-phosphane complexes, stabilized by dithiocarbamate ligands with known tumoricidal properties, that exhibited potent antiproliferative activities against A2780 and A2780cis ovarian carcinoma cell lines in vitro, 20- to 150-fold more cytotoxic than cisplatin. The anticancer mechanism of action of the lead Au(I)-phosphane compound were determined to be ROS-mediated, specifically via the intracellular accumulation of hydroxyl radical species. We further showed that the Au(I)-phosphane complex inflicted ER stress and stalled DNA synthesis, leading to apoptotic cell death, thereby circumventing resistance mechanisms to cisplatin treatment. In the present study, we proposed to examine the in vivo studies of these potential anticancer gold(I) complexes (1 and 2) on mice. The findings of the study will enhance the knowledge and understanding of these complexes along with their effect in mice. Also, will help in the development of a new generation of anticancer drugs with fewer side effects than other drugs of cisplatin currently available in the market