Arachidonic acid induces apoptosis in hematopoietic cells

M. T. Rizzo, E. Remzzi, B. Savoldi, L. Akard, M. Dumm, J. Thompson, D. English, V. Rizzoli, C. Carlo-Stella

Research output: Contribution to journalArticlepeer-review

Abstract

Arachidonic acid plays a crucial role as an intracellular messenger of a wide array of cellular responses. The present investigation was undertaken to examine the effect of arachidonic acid on the in vitro growth of normal and leukemic hematopoietic progenitor cells. Exposure of normal bone marrow progenitor cells to arachidonic acid (100 uM for 18 hrs) induced a 28%, 25% and 13. 5% inhibition of colony-forming unit-mix (CPU-Mix), colony-forming unit-granulocyte-macrophage(CFU-GM) and burst forming unit-erythroid (BFU-E), respectively. When progenitor cells obtained from chronic myeloid leukemia (CML) were preincubated with AA (100 nM for 18 hrs), a 33%, 45% and 26. 6% inhibition of CPU-Mix, BFU-E and CFUGM was observed. The effect of arachidonic acid was also investigated on long term culture-initiating cells (LTC-IC) from normal and CML bonemarrow. These experiments showed that arachidonic acid induced a greater inhibition of CML LTC-IC as compared to normal LTC-IC. To further examine the effect of arachidonic acid on leukemic cells , the bcr-abl transfected cell lines MO316 and 32D LG7 were incubated with different concentrations of arachidonic acid (10-100 uM) for 72 hrs and their growth rate was subsequently evaluated. Exposure to arachidonic acid induced a marked inhibition of cell proliferation. The ability of arachidonic acid to induce growth inhibition was not reversed by co-incubation with cycloxygenase and lipoxygenase inhibitors suggesting that the effect of the fatty acid was not mediated by arachidonic acid metabolites. Arachidonateinduced inhibition of cell growth was associated with induction of apoptosis. Exposure of CML progenitors and bcr-abl transfected cells to arachidonic acid induced endonucleosomal DNA breakdown as assayed by DNA electrophoresis and terminal deoxynucleotidyl transferase reaction. Taken together, these results suggest that arachidonic acid induces inhibition of hematopoietic cell growth by a mechanism involving apoptotic cell death.

Original languageEnglish
Pages (from-to)755
Number of pages1
JournalExperimental Hematology
Volume25
Issue number8
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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