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
Uses
RSL3 ((1S,3R)-RSL3) is an inhibitor of glutathione peroxidase 4 (GPX4) (ferroptosis activator), reduces the expression of GPX4 protein, and induces ferroptotic death of head and neck cancer cell. RSL3 increases the expression of p62 and Nrf2 and inactivates Keap1 in HN3-rslR cells[1].
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].
in vivo
RSL3 (100 mg/kg, Intratumorally twice per week for 20 days) significantly inhibits the growth of tumor in combination with Trigonelline (HY-N0414) in mice bearing HN3R cells[1].
| Animal Model: | Ten-week-old athymic BALB/c male nude mice (nu/nu) bearing HN3R cells[1] |
| Dosage: | 100 mg/kg in combination with trigonelline (50 mg/kg) |
| Administration: | Intratumorally twice per week for 20 days |
| Result: | Significantly reduced the volume of tumor combined with trigonelline in mice. |
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
