Fig. 8

Sulfasalazine synergistically enhances the anti-cancer activity of Metformin in vivo. A Athymic nude mice were orthotopically injected with T47D cells and treated with metformin (200 mg/kg, three weeks) daily in drinking water with or without sulfasalazine administration via intraperitoneal injection until the end of the experiment. Tumor volumes are shown relative to the initial volume measured before treatment (n = 5 mice/group). B Representative isolated tumor images from each treatment group at day 21 after treatment are shown. C Representative images of immunohistochemical staining (SLC7A11, UFM1 and 4-HNE) of T47D cell-derived xenograft tumors with the indicated treatments. The box graphs show the quantification of IHC staining. Chi-square test was used for statistical analysis. D Schematic diagram showing metformin regulation of ferroptosis. SLC7A11 can be modified by UFM1; metformin exerts its anti-cancer effect by inhibiting UFMylation of SLC7A11 leading to ferroptosis in an AMPK-independent manner