The accumulation of Fe2+ and upregulation of HO-1 are involved in Lut-induced cell death in ccRCC. Levels of intracellular ferrous Fe2+ (a) and GSH (b) of 786-O and OS-RC-2 cells treated with or without Lut for 24 h or 48 h. (c) The LDH release assay showed that Lut-induced cell death of ccRCC was alleviated in the presence of DFP, NAC, and Fer-1 and was exacerbated in the presence of FAC. (d) Expression levels of MMP2, vimentin, E-cadherin, HO-1, KEAP1, NRF2, GPX4, SLC7A11, SLC40A1, DMT1, FTL, and FTH1 in 786-O and OS-RC-2 cells treated with or without Lut for 24 h as determined by western blot analysis. (e) Semiquantification of band densities in (d). The data in (a), (b), (c), and (e) are expressed as the mean ± SD. ∗P < 0.05 vs. the NC group, #P < 0.05 vs. Lut group. Lut: luteolin; DFP: deferiprone; NAC: acetylcysteine; Fer-1: ferrostatin-1; FAC: ammonium iron (III) citrate.