However, Koike et al. first proved that H2S can also activate the NRF2 pathway in cancer cells, since the polysulfide N2S4, a product of H2S signaling, was found to protect Neuro2A NB cells from the cytotoxic effects of tert-butyl hydroperoxide (t-BHP), promoting an increased GSH synthesis and HO-1 expression due to KEAP1 inactivation and enhanced NRF2 nuclear translocation [127]. The gene discussed is NFE2L2; the disease is cancer.