GCLC and cancer: High levels of NRF2 protect cancer cells from the effects of various chemotherapeutic drugs, whereas knockdown of NRF2, transiently or stably, increases the sensitivity of cancer cells to chemotherapeutic-induced cell death [58] In the present study DOX significantly down-regulated the expression of NRF2 (−2.085), GST (−1.923), GCL (−1.776) and HO (−2.849) in the hearts and down-regulated GCLC, GSTM1, GSTM2, GSTM5, GSTK1K1, NFE2L2, CBR1, all of which could be related both to the cardiotoxicity and anti-cancer efficiency of DOX.