Docosahexaenoic acid induces apoptosis in Jurkat cells by a protein phosphatase-mediated process

Docosahexaenoic acid (DHA) is an omega-3 fatty acid under intense investiga tion for its ability to modulate cancer cell growth and survival. This rese arch was performed to study the cellular and molecular effects of DHA. Our experiments indicated that the treatment of Jurkat cells with DHA inhibited their survival, whereas similar concentrations (60 and 90 muM) of arachido nic acid and oleic acid had little effect. To explore the mechanism of inhi bition, we used several measures of apoptosis to determine whether this pro cess was involved in DHA-induced cell death in Jurkat cells. Caspase-3, an important cytosolic downstream regulator of apoptosis, is activated by deat h signals through proteolytic cleavage. Incubation of Jurkat cells with 60 and 90 mu \M DHA caused proteolysis of caspase-3 within 48 and 24 h, respec tively. DHA treatment also caused the degradation of poly-ADP-ribose polyme rase and DNA fragmentation as assayed by flow cytometric TUNEL (terminal de oxynucleotidyl transferase-mediated dUTP nick end labeling) assay. These re sults indicate that DHA induces apoptosis in Jurkat leukemic cells. DHA-ind uced apoptosis was effectively inhibited by tautomycin and cypermethrin at concentrations that affect protein phosphatase 1 (PP1) and protein phosphat ase 2B (PP2B) activities, respectively, implying a role for these phosphata ses in the apoptotic pathway. Okadaic acid, an inhibitor of protein phospha tase 2A, had no effect on DHA-induced apoptosis. These results suggest that one mechanism through which DHA may control cancer cell growth is through apoptosis involving PP1/PP2B protein phosphatase activities. (C) 2001 Elsev ier Science B.V. All rights reserved.