Botanical sulfane sulfur donors inhibit ferroptotic cell death caused by the depletion of cysteine

•Botanical trisulfide compounds function as a sulfane sulfur donor.•Glutathione depletion is not responsible for the ferroptotic cell death.•Ferroptosis seems to be caused by the lowering sulfane sulfur production.•Squeezes of garlic and cabbage prevent the ferroptotic cell death.•Diallyl trisulfide and dimethyl trisulfide prevent the ferroptotic cell death. Inhibitors against cystine-glutamate antiporter, including erastin, elicit ferroptotic cell death. The erastin-induced ferroptotic cell death appears to be caused by cysteine as well as glutathione depletion. Cysteine is an essential substrate for sulfane sulfur producing systems in cells, generating persulfides that function as intracellular antioxidants and intermediates in iron-sulfur cluster production. Therefore, we examined whether botanical sulfane sulfur donors such as diallyl trisulfide (DATS) and dimethyl trisulfide (DMTS) prevent ferroptotic cell death in HT1080 cells treated with erastin. As a result, DMTS (20 μM) and DATS (10 μM) rescued the erastin-treated HT1080 cells by 69.6% and 91.6%, respectively. Furthermore, DMTS-containing squeeze of cabbage (2.0 g/L) and DATS-containing squeeze of garlic (0.07 g/L) rescued the erastin-treated HT1080 cells by 76.5% and almost 100%, respectively. In conclusion, the ingestion of trisulfides may bring about increased resistance to ferroptotic cell death in vivo.