n-3 Polyunsaturated fatty acids induce acute myeloid leukemia cell death associated with mitochondrial glycolytic switch and Nrf2 pathway activation

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Frédéric PicouEmmanuel Gyan

Abstract

Acute Myeloid Leukemia (AML) remains a therapeutic challenge and improvements in chemotherapy are needed. n-3 polyunsaturated fatty acids (PUFAs), present in fish oil (FO) at high concentrations, have antitumoral properties in various cancer models. We investigated the effects of two n-3 PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in AML cell lines and primary AML blasts. EPA and DHA induced a dose-dependent decrease in cell viability in five AML cell lines, which was also observed with FO, but not SO (devoid of n-3 PUFAs) in cell lines and primary leucoblasts. Mitochondrial energy metabolism shifted from oxidative respiration to glycolytic metabolism in the U937, MOLM-13, and HL-60 cell lines. This phenomenon was associated with major disorganization of the mitochondrial network and mitochondrial swelling. Transcriptomic analysis after 6 h and 24 h of exposure to FO revealed a Nrf2 activation signature, which was confirmed by evidence of Nrf2 nuclear translocation in response to oxidative stress, but insufficient to prevent cell death following prolonged exposure. Apoptosis studies showed consistent phosphatidylserine exposition among the AML cell lines tested and a reduced mitochondrial membrane potenti...Continue Reading

Citations

Jun 13, 2020·International Journal of Molecular Sciences·Bianka BojkováMagdalena Wszedybyl-Winklewska
Jan 13, 2021·Seminars in Cancer Biology·Alfonso Varela-LópezJosé L Quiles
Sep 29, 2019·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·Esmaeil MortazJohan Garssen
Aug 23, 2020·Free Radical Biology & Medicine·Ignacio A Cortés FuentesJuan G Gormaz
Jan 27, 2021·Journal of Agricultural and Food Chemistry·Guiling LiJingwen Liu

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