Abstract
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.
Highlights
Malignant melanoma is a highly aggressive type of skin cancer that metastasizes to almost any internal organ; the incidence of melanoma has increased steadily over the past three decades[1]
The effect of methyl jasmonate (MJ) and COR on the growth of melanoma cells or normal melanocytes was investigated by assessing the viability of HEMn-LP, A375, and A2058 cells treated with different doses of MJ and COR for 24 h by performing 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide (MTT) assay
To validate the antiproliferative effect of COR on melanoma cells, we examined the changes in A375 and A2058 cell proliferation after treatment with the combination of COR and 2-DG by performing 5′-bromo-2′-deoxyuridine (BrdU) incorporation enzyme-linked immunosorbent assay (ELISA)
Summary
Malignant melanoma is a highly aggressive type of skin cancer that metastasizes to almost any internal organ; the incidence of melanoma has increased steadily over the past three decades[1]. Plant hormones play a pivotal role in regulating defensive responses to invading pathogens by triggering programmed cell death (PCD) near the infection site[10]. The transgenic expression of antior proapoptotic proteins (Bcl-xL, Ced-9, p35, or Bax) affects the suppression or activation of cell death in plants cells similar to that in animal cells. Plant hormones such as abscisic acid, salicylic acid, and jasmonic acid regulate PCD and exhibit anticancer activities both in vitro www.nature.com/scientificreports/. Methyl jasmonate (MJ), a plant stress hormone belonging to jasmonic acid family, induces cell death in and impairs the metastasis of various cancers such as breast, lung, and gastric cancers and melanoma[15,16,17,18]. Recent studies have identified biomarkers and therapeutic targets in lung, breast, ovarian, and colon cancers and melanoma using analytical techniques in metabolomics and have evaluated the effects of therapeutic compounds by assessing key metabolic changes in colorectal cancer and melanoma[27,28,29,30,31,32,33,34]
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