Specificity of arachidonic acid-induced inhibition of growth and activation of c-jun kinases and p38 mitogen-activated protein kinase in hematopoietic cells.
We demonstrated that arachidonic acid inhibits growth and induces apoptosis in the bcr-abl transformed leukemia cell line, H7.bcr-abl A54 and in human chronic myeloid leukemia hematopoietic cells. This investigation was undertaken to determine the cell-type specificity of this response. We compared the effect of arachidonic acid on H7.bcr-abl A54 cells to Jurkat (human acute T-cell leukemia), U937 (human histiocytic lymphoma) and RPMI 7666 (human normal B-lymphoblasts) cells. Arachidonic acid (100 microM, 72 h) inhibited growth of H7.bcr-abl A54, Jurkat and U937 cells by 82.2, 67.5 and 20%, respectively, but had no effect on RPMI 7666 cells. These effects were investigated in relationship to the activation of p38 mitogen activated protein kinase (p38 MAPK) and c-jun amino-terminal kinase (JNK) by arachidonic acid in these cell lines. Results from these studies suggest that signaling and proliferative responses to arachidonic acid are cell-type specific. Leukemia cells appear to be more sensitive to the antiproliferative effect of arachidonic acid than normal cells.
Rizzo
Maria Teresa
MT
Signal Transduction Laboratory, Methodist Research Institute, Clarian Health Partners Inc., Indianapolis, IN 46202, USA. mrizzo@clarian.org
Pudlo
Nancy
N
Farrell
Lindsey
L
Leaver
Anne
A
D016718:Arachidonic Acid / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015118:Eicosapentaenoic Acid; D004789:Enzyme Activation / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007938:Leukemia / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
D005231:Fatty Acids, Unsaturated; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases