Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review

Milad Moloudizargari, Esmaeil Mortaz _, Mohammad Hossein Asghari, Ian M. Adcock, Frank A. Redegeld and Johan Garssen

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Oncotarget. 2018; 9:11858-11875. https://doi.org/10.18632/oncotarget.24405

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Milad Moloudizargari1, Esmaeil Mortaz2,3,4, Mohammad Hossein Asghari5, Ian M. Adcock6, Frank A. Redegeld4 and Johan Garssen4,7

1Department of Immunology, School of Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3Clinical Tuberculosis and Epidemiology Research Center, National Research Institute for Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

4Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands

5Department of Pharmacology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran

6Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, UK

7Nutricia Research Centre for Specialized Nutrition, Utrecht, Netherlands

Correspondence to:

Esmaeil Mortaz, email: [email protected]

Keywords: omega-3; eicosapentaenoic acid; docosahexaenoic acid; apoptosis; fish oil

Received: August 30, 2017    Accepted: January 21, 2018    Published: February 05, 2018


Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo, following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms have been proposed for the anti-cancer effects of these omega-3 PUFAs; however, the exact mechanisms still remain unknown. While numerous studies have investigated the effects of DHA and EPA on solid tumors and the responsible mechanisms, there is no consensus regarding the effects and mechanisms of action of these two FAs in hematological malignancies. Here, we performed a systematic review of the beneficial effects of EPA and DHA on hematological cell lines as well as the findings of related in vivo studies and clinical trials. We summarize the key underlying mechanisms and the therapeutic potential of these PUFAs in the treatment of hematological cancers. Differential expression of apoptosis-regulating genes and Glutathione peroxidase 4 (Gp-x4), varying abilities of different cancerous and healthy cells to metabolize EPA into its more active metabolites and to uptake PUFAS are among the major factors that determine the sensitivity of cells to DHA and EPA. Considering the abundance of data on the safety of these FAs and their proven anti-cancer effects in hematological cell lines and the lack of related human studies, further research is warranted to find ways of exploiting the anticancer effects of DHA and EPA in clinical settings both in isolation and in combination with other therapeutic regimens.

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