Abstract

Τhe effect of docosahexaenoic acid (DHA, an omega-3 polyunsaturated fatty acid) upon the proliferation of EoL-1 (Eosinophilic leukemia) cell line was assessed, while additional cellular events during the antiproliferative action were recorded. DHA inhibited EoL-1 cells growth dose-dependently by inducing growth arrest at G0/1 phase of the cell cycle. After DHA addition to the cells, the expression of MYC oncogene was decreased, PTAFR-mRNA overexpression was observed which was used as a marker of differentiation, and PLA2G4A-mRNA increase was recorded. The enzymatic activities of phospholipase A2 (PLA2), a group of hydrolytic enzymes, whose action precedes and leads to PAF biosynthesis through the remodeling pathway, as well as platelet activating factor acetylhydrolase (PAFAH) which hydrolyses and deactivates PAF, were also measured. DHA had an effect on the levels of both the intracellular and secreted activities of PLA2 and PAFAH. The inflammatory cytokines IL-6 and TNF-α were also detected in high levels. In conclusion, DHA-induced EoL-1 cells differentiation was correlated with downregulation of MYC oncogene, overexpression of PTAFR and PLA2G4A-mRNAs, increase of the inflammatory cytokines production, and alteration of the enzymatic activities that regulate PAF levels. DHA is a natural substance and the understanding of its action on EoL-1 cells on molecular level could be useful in further investigation as a future therapeutic tool against F/P + hypereosinophilic syndrome.

Highlights

  • Docosahexaenoic acid (DHA) is a highly polyunsaturated omega-3 fatty acid (ω-3 or n-3).Omega-3 polyunsaturated fatty acids (PUFAs) are essential fatty acids which must be obtained from nutrition

  • In order to clarify whether DHA inhibited the proliferation of EoL-1 cells, the number of DHA-treated cells in certain time points and various DHA concentrations was counted by trypan blue staining

  • We demonstrated for the first time the antiproliferative and differentiating effects of docosahexaenoic acid on the EoL-1 leukemic cell line

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Summary

Introduction

Docosahexaenoic acid (DHA) is a highly polyunsaturated omega-3 fatty acid (ω-3 or n-3).Omega-3 polyunsaturated fatty acids (PUFAs) are essential fatty acids which must be obtained from nutrition. Omega-3 fatty acids (FAs) are considered necessary for human health because, esterified in phospholipids, they participate in cell membranes structure, they affect the function of cell membrane receptors and regulate gene function [2]. They are precursors of hormones [3]. Regulating blood clotting, contraction, and relaxation of artery walls, and inflammation, among others Due to these effects, omega-3 fats have been shown to help prevent heart disease and stroke, resolve inflammation [4], and may play protective roles in cancer [5] and other diseases

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