International Journal of Medical Sciences

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16 December 2018

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Int J Med Sci 2018; 15(12):1296-1303. doi:10.7150/ijms.27326

Research Paper

Eicosapentaenoic acid reduces indoleamine 2,3-dioxygenase 1 expression in tumor cells

Chih-Chiang Wang1, Chih-Jen Yang2,3,4, Li-Hsien Wu5, Han-Chen Lin6, Zhi-Hong Wen7, Che-Hsin Lee8,9✉

1. Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
2. Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
3. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
4. Faculty of Medicine, Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Taiwan
5. Department of Public Health, China Medical University, Taichung, Taiwan
6. Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
7. Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan
8. Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
9. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.

Abstract

Marine plants and animals have omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA is required for biological processes, but humans are unable to synthesize them and must be obtained from dietary sources. EPA has been used as an antitumor agent but the molecular mechanisms for the regulation of tumor microenvironment immunity by EPA are still unknown. The indoleamine 2,3-dioxygenase 1 (IDO) catalyzes conversion of tryptophan to kynurenine to induce immune evasion in tumor microenvironment. In this study, EPA inhibited the expression of IDO via downregulation of protein kinase B (Akt)/mammalian targets of rapamycin (mTOR) signaling pathway in tumor cells. Meanwhile, a significant decrease in kynurenine levels and increase in T cell survival were observed after tumor cells treated with EPA. The results demonstrated that EPA can activate host antitumor immunity by inhibiting tumor IDO expression. Therefore, our finding suggests that EPA can be enormous potential for cancer immunotherapy.

Keywords: Eicosapentaenoic acid, tumor microenvironment, indoleamine 2,3-dioxygenase, immune evasion, immunotherapy

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How to cite this article:
Wang CC, Yang CJ, Wu LH, Lin HC, Wen ZH, Lee CH. Eicosapentaenoic acid reduces indoleamine 2,3-dioxygenase 1 expression in tumor cells. Int J Med Sci 2018; 15(12):1296-1303. doi:10.7150/ijms.27326. Available from http://www.medsci.org/v15p1296.htm