An omega-3 polyunsaturated fatty acid derivative, 18-HEPE, protects against CXCR4-associated melanoma metastasis

Jieping Li, Chih Yu Chen, Makoto Arita, Kuijin Kim, Xiangyong Li, Hongman Zhang, Jing X. Kang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Melanoma has a high propensity to metastasize and exhibits a poor response to classical therapies. Dysregulation of the chemokine receptor gene CXCR4 is associated with melanoma progression, and although n-3 polyunsaturated fatty acids (PUFAs) are known to be beneficial for melanoma prevention, the underlying mechanism of this effect is unclear. Here, we used the n-3 fatty acid desaturase (Fat-1) transgenic mouse model of endogenous n-3 PUFA synthesis to investigate the influence of elevated n-3 PUFA levels in a mouse model of metastatic melanoma. We found that relative to wild-type (WT) mice, Fat-1 mice exhibited fewer pulmonary metastatic colonies and improved inflammatory indices, including reduced serum tumor necrosis factor alpha (TNF-α) levels and pulmonary myeloperoxidase activity. Differential PUFA metabolites in serum were considered a key factor to alter cancer cell travelling to lung, and we found that n-6 PUFAs such as arachidonic acid induced CXCR4 protein expression although n-3 PUFAs such as eicosapentaenoic acid (EPA) decreased CXCR4 levels. In addition, serum levels of the bioactive EPA metabolite, 18-HEPE, were elevated in Fat-1 mice relative to WT mice, and 18-HEPE suppressed CXCR4 expression in B16-F0 cells. Moreover, relative to controls, numbers of pulmonary metastatic colonies were reduced in WT mice receiving intravenous injections either of 18-HEPE or 18-HEPE-pretreated melanoma cells. Our results indicate that 18-HEPE is a potential anticancer metabolite that mediates, at least in part, the preventive effect of n-3 PUFA on melanoma metastasis.

Original languageEnglish
Pages (from-to)1380-1388
Number of pages9
JournalCarcinogenesis
Volume39
Issue number11
DOIs
Publication statusPublished - 2018 Dec 13
Externally publishedYes

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Omega-3 Fatty Acids
Unsaturated Fatty Acids
Melanoma
Neoplasm Metastasis
Lung
Eicosapentaenoic Acid
Fats
Serum
Fatty Acid Desaturases
Chemokine Receptors
Arachidonic Acid
Intravenous Injections
Transgenic Mice
Peroxidase
Tumor Necrosis Factor-alpha
Genes
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research

Cite this

An omega-3 polyunsaturated fatty acid derivative, 18-HEPE, protects against CXCR4-associated melanoma metastasis. / Li, Jieping; Chen, Chih Yu; Arita, Makoto; Kim, Kuijin; Li, Xiangyong; Zhang, Hongman; Kang, Jing X.

In: Carcinogenesis, Vol. 39, No. 11, 13.12.2018, p. 1380-1388.

Research output: Contribution to journalArticle

Li, Jieping ; Chen, Chih Yu ; Arita, Makoto ; Kim, Kuijin ; Li, Xiangyong ; Zhang, Hongman ; Kang, Jing X. / An omega-3 polyunsaturated fatty acid derivative, 18-HEPE, protects against CXCR4-associated melanoma metastasis. In: Carcinogenesis. 2018 ; Vol. 39, No. 11. pp. 1380-1388.
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