Ozonated olive oil inhibits melanoma proliferation by inducing ferroptosis

Although ozone is a potent oxidant that can damage lungs and skin after prolonged exposure, ozonated olive oil (OZO) exhibits antimicrobial, anti-inflammatory, and wound-healing effects. Here, we describe a novel application of OZO in melanoma therapy. Treatment with OZO markedly inhibited the proliferation of both human and murine melanoma cells, while sparing normal human keratinocyte. At the molecular level, OZO upregulated ferroptosis-related genes, decreased intracellular glutathione (GSH) and GPX4 protein levels and accelerated lipid peroxidation. Critically, OZO-induced growth inhibition in melanoma cells was prevented by ferroptosis inhibitors (ferrostatin-1 and deferiprone), but not by inhibitors of apoptosis or necroptosis. Taken together, these findings offer new therapeutics strategy for treating melanoma by inducing ferroptosis.