Luteolin triggers autophagy-dependent ferroptosis via suppressing SLC40A1-related Fe2+ efflux in hepatocellular carcinoma (HCC)

BACKGROUND: transport, remains unclear. METHODS: levels, lipid reactive oxygen species (ROS) production, and glutathione (GSH) content. Autophagy was determined by analyzing the LC3B-II/LC3B-I ratio, p62 expression and some autophagy-related genes via Western blot, as well as LC3 puncta formation using immunofluorescence. The expression of SLC40A1 was detected by qPCR. SLC40A1 overexpression and knockdown models were established to verify its role in luteolin-induced effects in vivo and in vitro. RESULTS: accumulation and ferroptosis, while SLC40A1 knockdown mimicked the effects of luteolin. In vivo, luteolin suppressed xenograft tumor growth, enhanced autophagy, induced ferroptosis, and downregulated SLC40A1 expression in tumor tissues. CONCLUSION: export. This study uncovers a novel anti-tumor mechanism of luteolin, providing a potential therapeutic strategy for HCC treatment by targeting SLC40A1-mediated iron homeostasis and the crosstalk between autophagy and ferroptosis.