Title: 5-Oxo-ETE analogs and the proliferation of cancer cells.
Authors: O'Flaherty, Joseph T; Rogers, LeAnn C; Paumi, Christian M; Hantgan, Roy R; Thomas, Lance R; Clay, Carl E; High, Kevin; Chen, Yong Q; Willingham, Mark C; Smitherman, Pamela K; Kute, Timothy E; Rao, Anuradha; Cramer, Scott D; Morrow, Charles S
Published In Biochim Biophys Acta, (2005 Oct 1)
Abstract: MDA-MB-231, MCF7, and SKOV3 cancer cells, but not HEK-293 cells, expressed mRNA for the leukocyte G protein-coupled 5-oxo-eicosatetraenoate (ETE) OXE receptor. 5-Oxo-ETE, 5-oxo-15-OH-ETE, and 5-HETE stimulated the cancer cell lines but not HEK-293 cells to mount pertussis toxin-sensitive proliferation responses. Their potencies in eliciting this response were similar to their known potencies in activating leukocytes and OXE receptor-transfected cells. However, high concentrations of 5-oxo-ETE and 5-oxo-15-OH-ETE, but not 5-HETE, arrested growth and caused apoptosis in all four cell lines; these responses were pertussis toxin-resistant. The same high concentrations of the oxo-ETEs but again not 5-HETE also activated peroxisome proliferator-activated receptor (PPAR)-gamma. Pharmacological studies indicated that this activation did not mediate their effects on proliferation. These results are the first to implicate the OXE receptor in malignant cell growth and to show that 5-oxo-ETEs activate cell death programs as well as PPARgamma independently of this receptor.
PubMed ID: 16154383
MeSH Terms: Anilides/pharmacology; Apoptosis/drug effects; Arachidonic Acids/metabolism; Arachidonic Acids/pharmacology*; Binding Sites/genetics; Caspase 3; Caspases/metabolism; Cell Line; Cell Line, Tumor; Cell Proliferation/drug effects*; Cell Survival/drug effects; Gene Expression/genetics; Humans; Hydroxyeicosatetraenoic Acids/metabolism; Hydroxyeicosatetraenoic Acids/pharmacology; Mitosis/drug effects; PPAR gamma/antagonists & inhibitors; PPAR gamma/genetics; PPAR gamma/metabolism; Peroxisome Proliferator-Activated Receptors/genetics; Pertussis Toxin/pharmacology; Poly(ADP-ribose) Polymerases/metabolism; Prostaglandin D2/analogs & derivatives; Prostaglandin D2/metabolism; Prostaglandin D2/pharmacology; Protein Binding; Receptors, Eicosanoid/genetics; Receptors, Eicosanoid/physiology*; Transfection