Description
RSL3 (1219810-16-8) Inhibits glutathione peroxidase (GPX4) inducing ferroptosis.1,2? Effectively induces ferroptosis in glioblastoma cells.3? Everolimus in combination with RSL3 synergistically inhibits the viability of renal cell carcinoma (RCC) cells suggesting a mechanism by which RCC drug resistance may be overcome.4
in vitro
rsl3, which was a glutathione peroxidase (gpx) 4 inhibitor, had been cooperated with the smac mimetic bv6 to induce reactive oxygen species (ros)-dependent cell death in acute lymphoblastic leukemia cells. it was found that addition of the caspase inhibitor failed to rescue ros-induced cell death, suggesting that rsl3-induced cell death occured in a caspase-independent manner. moreover, the iron chelator deferoxamine inhibited rsl3/bv6-induced cell death significantly, however, it could not rescue cell death by erastin/bv6, indicating that rsl3/bv6-, but not erastin/bv6-mediated cell death depended on iron. in addition, it was shown that ros production was required for both rsl3/bv6- and erastin/bv6-induced cell death. in contrast, genetic or pharmacological inhibition of lipid peroxidation by gpx4 overexpression significantly decreased rsl3/bv6-induced cell death. of importance, inhibition of lipid peroxidation could protect from rsl3/bv6-stimulated ros production [1].
References
Yang et al. (2014), Regulation of ferroptotic cancer cell death by GPX4; Cell 156 317
Kagan et al. (2017), Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis; nAT. Chem. Biol. 13 81
Shengbiao et al. (2021), RSL3 Drives Ferroptosis through NF-kB Pathway Activation and GPX4 depletion in Glioblastoma; oXID. Med. Cell. Longev. 2021 2915019
Yangyun et al. (2022), Everolimus accelerates Erastin and RSL3-induced ferroptosis in renal cell carcinoma; Gene 809 145992
