Here, the use of siRNA against CUL3 in MCF-7 breast cancer cells increased the levels of NRF2-regulated proteins, including GCL, NQO1, AKR1C1, UGDH, TXN and the drug transporter ABCC1, ultimately conferring a resistance to the oxidants and conventional anticancer agents. Here, AKR1C1 is linked to breast carcinoma.