Novel insights into redox-based mechanisms for auranofin- induced rapid cancer cell death

One of the significant features of cancer cells is a persistent pro-oxidative status. Therefore, compared to their normal counterparts, the malignant cells are generally more dependent on antioxidants for cell survival and more vulnerable to further oxidative insults via pharmacolog-ical interventions targeting cellular redox systems. This is the biological basis of oxidative stress- or redox-based anticancer strategies. Auranofin (AUF) is a promising repositioning anti-cancer molecule with a multifaceted mode of action that could be cancer cell type- or dose-dependent. Using triple-negative breast cancer cells, we evidenced that thioredoxin reduc-tase inhibition, the best-studied anticancer activity of AUF, is not sufficient to induce efficient cell death. Cytotoxic doses of AUF trigger rapid and global intracellular oxidative stress. Based on the indications from redox proteome data, we showed experimentally that AUF treatment triggered a dose-dependent S-phase arrest and disintegration of actin cytoskeleton structure. These findings on AUF-induced early effects should provide novel insights into the anticancer mechanisms of this promising molecule