Activation of the reverse transsulfuration pathway through NRF2/CBS confers erastin-induced ferroptosis resistance

摘要

Lethal dose of erastin induces ferroptosis resistance in ovarian cancer cells. a SKOV3, OVCA429 cells were sensitive to erastin-induced death. SKOV3, OVCA429 cells were treated with erastin (0, 5, 10 and 20 μM) for the indicated time points, and cell viability was analysed. b Fer-1, Lip-1, DFO, NAC and Trolox rescued erastin-induced death, confirming erastin-induced ferroptosis in SKOV3 and OVCA429 cells. Cells were treated with erastin in the absence or presence of indicated inhibitors (Fer-1, Lipo-1, BSO, NAC, Troxl, z-VAD-FMK, NAS and Nec-1s) for 24 h, and cell viability was assayed, ***p < 0.0001. c Outline of the establishment of SKOV3 and OVCA429 erastin-resistant cells. d SKOV3 Era-R cells were resistant to lethal dosage of erastin. SKOV3 and SKOV3 Era-R cells were treated with erastin 20 μM for 24 h. Cell viability was monitored by light microscopy (scale bar = 400 μm, magnification: ×10). e SKOV3 Era-R, OVCA429 Era-R cells were resistant to erastin insult. Cells were treated with erastin (0, 10, 20 and 40 μM) for 72 h, and cell viability was examined, ***p < 0.0001. f SKOV3, SKOV3 Era-R, OVCA429 and OVCA429 Era-R cells were either untreated or treated with SAS (1 mM), RSL (1 μM) or FIN56 (5 μM) for the indicated time, cell viability was examined. **p < 0.001, ***p < 0.0001 as compared with untreated control.