Abstract

Rosemary essential oil (REO) is widely recognized as a popular natural product because of its antioxidant, antibacterial, and anti-inflammatory properties, but its role in cancer treatment remains relatively understudied. In light of melanoma’s status as one of the most hazardous tumors, this study employed GCMS to analyze three REOs, focusing on their antiproliferative effects and the underlying mechanisms in melanoma cells. Through multivariate analysis, active components associated with cytotoxicity were identified, with the ‘Dutch Mill’ REO showing the strongest antiproliferative effect and selected for further investigation. The impacts on the cell cycle and death mechanisms were explored in B16-F10 cells, and quantitative proteomics revealed 165 differentially regulated proteins, some of which were significantly associated with ferroptosis. REO notably increased reactive oxygen species levels, decreased mitochondrial membrane potential, and elevated lipid peroxidation in B16-F10 cells. The qRTPCR results confirmed significant alterations in the ferroptosis pathway. Furthermore, the antiproliferative and ROS-promoting effects of REO were reversed by ferroptosis inhibitors. These findings highlight the promising potential of REO in health care and pharmaceuticals.

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