Metabolic and lipidomic investigation of the antiproliferative effects of coronatine against human melanoma cells

Melanoma is the most aggressive form of skin cancer, with metastatic melanoma being refractory to currently available conventional therapies. In this study, we evaluated the inhibitory effect of coronatine (COR) on the proliferation of metastatic melanoma cells. COR inhibited the proliferation of melanoma cells but negligibly affected the proliferation of normal melanocytes. Comparative metabolic and lipidomic profiling using gas chromatography-mass spectrometry and direct infusion-mass spectrometry was performed to investigate COR-induced metabolic changes. These analyses identified 33 metabolites and 82 lipids. Of these, the levels of lactic acid and glutamic acid, which are involved in energy metabolism, significantly decreased in COR-treated melanoma cells. Lipidomic profiling indicated that ceramide levels increased in COR-treated melanoma cells, suggesting that ceramides could function as a suppressor of cancer cell proliferation. In contrast, the levels of phosphatidylinositol (PI) species, including PI 16:0/18:0, 16:0/18:1, 18:0/18:0, and 18:0/18:1, which were found to be potential biomarkers of melanoma metastasis in our previous study, were lower in the COR-treated cells than in control cells. The findings of metabolomic and lipidomic profiling performed in the present study provide new insights on the anticancer mechanisms of COR and can be used to apply COR in cancer treatment.