The findings of the present study revealed that a novel water-soluble ruthenium(II)-curcumin compound (RuCUR) [42] was able to induce cancer cell death that correlated with mutp53 downregulation and with activation of wtp53; they also revealed a resistance mechanism via the NRF2-induced antioxidant system likely enhanced by ROS reduction. This evidence concerns the gene NFE2L2 and cancer.