Our results provide first ChIP binding evidence that NRF2 bound at transcriptional target gene AIFM2, and ZVI-NP treatment reduced the NRF2-mediated expression of AIFM2. In fact, transient NRF2 activation can protect cell from external stress; however, persistent NRF2 activation in cancer cells (known as NRF2 addiction) confers therapeutic resistance and aggressive tumorigenicity 39, 40. Here, NFE2L2 is linked to cancer.