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

R. A. Siddiqui, L. J. Jenski, K. Neff, K. Harvey, R. J. Kovacs, W. Stillwell

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

Docosahexaenoic acid (DHA) is an omega-3 fatty acid under intense investigation for its ability to modulate cancer cell growth and survival. This research 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 μM) of arachidonic acid and oleic acid had little effect. To explore the mechanism of inhibition, we used several measures of apoptosis to determine whether this process was involved in DHA-induced cell death in Jurkat cells. Caspase-3, an important cytosolic downstream regulator of apoptosis, is activated by death signals through proteolytic cleavage. Incubation of Jurkat cells with 60 and 90 μM DHA caused proteolysis of caspase-3 within 48 and 24 h, respectively. DHA treatment also caused the degradation of poly-ADP-ribose polymerase and DNA fragmentation as assayed by flow cytometric TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay. These results indicate that DHA induces apoptosis in Jurkat leukemic cells. DHA-induced apoptosis was effectively inhibited by tautomycin and cypermethrin at concentrations that affect protein phosphatase 1 (PP1) and protein phosphatase 2B (PP2B) activities, respectively, implying a role for these phosphatases in the apoptotic pathway. Okadaic acid, an inhibitor of protein phosphatase 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.

Original languageEnglish (US)
Pages (from-to)265-275
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1499
Issue number3
DOIs
StatePublished - Jan 15 2001

Keywords

  • Apoptosis
  • Caspase-3
  • Docosahexaenoic acid
  • Jurkat cell
  • Protein phosphatase

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biophysics

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