College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
Sci Rep. 2019 Feb 28;9(1):3140. doi: 10.1038/s41598-019-39990-w.
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.
黑色素瘤是最具侵袭性的皮肤癌,转移性黑色素瘤对目前可用的常规疗法具有抗性。在这项研究中,我们评估了冠菌素 (COR) 对转移性黑色素瘤细胞增殖的抑制作用。COR 抑制黑色素瘤细胞的增殖,但对正常黑素细胞的增殖影响可以忽略不计。使用气相色谱-质谱联用和直接进样-质谱联用进行比较代谢组学和脂质组学分析,以研究 COR 诱导的代谢变化。这些分析鉴定出 33 种代谢物和 82 种脂质。其中,参与能量代谢的乳酸和谷氨酸水平在 COR 处理的黑色素瘤细胞中显著降低。脂质组学分析表明,COR 处理的黑色素瘤细胞中的神经酰胺水平增加,表明神经酰胺可以作为抑制癌细胞增殖的物质。相比之下,我们之前的研究发现,PI 16:0/18:0、16:0/18:1、18:0/18:0 和 18:0/18:1 等 PI 物种的水平在 COR 处理的细胞中低于对照细胞,这些 PI 物种被认为是黑色素瘤转移的潜在生物标志物。本研究进行的代谢组学和脂质组学分析结果为 COR 的抗癌机制提供了新的见解,并可用于将 COR 应用于癌症治疗。