title: 5-Oxo-ETE analogs and the proliferation of cancer cells.
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.
authors.affiliation: Department of Internal Medicine, Section on Infectious Diseases, Wake Forest University Medical Center, Medical Center Boulevard, Winston-Salem, NC 27156, USA. joflaher@wfubmc.edu
authors.forename: Joseph T
authors.initials: JT
authors.lastname: O'Flaherty
authors.forename: LeAnn C
authors.initials: LC
authors.lastname: Rogers
authors.forename: Christian M
authors.initials: CM
authors.lastname: Paumi
authors.forename: Roy R
authors.initials: RR
authors.lastname: Hantgan
authors.forename: Lance R
authors.initials: LR
authors.lastname: Thomas
authors.forename: Carl E
authors.initials: CE
authors.lastname: Clay
authors.forename: Kevin
authors.initials: K
authors.lastname: High
authors.forename: Yong Q
authors.initials: YQ
authors.lastname: Chen
authors.forename: Mark C
authors.initials: MC
authors.lastname: Willingham
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Smitherman
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Kute
authors.forename: Anuradha
authors.initials: A
authors.lastname: Rao
authors.forename: Scott D
authors.initials: SD
authors.lastname: Cramer
authors.forename: Charles S
authors.initials: CS
authors.lastname: Morrow
mesh_terms: D000813:Anilides / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites / Q000235:genetics; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics; D037342:Pertussis Toxin / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D018055:Receptors, Eicosanoid / Q000235:genetics / Q000502:physiology*; D014162:Transfection
chemical_list: C477819:15-deoxyprostaglandin J2; C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; C504018:OXER1 protein, human; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D018055:Receptors, Eicosanoid; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; C075441:5-oxo-15-hydroxy-6,8,11,13-eicosatetraenoic acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C037112:9-deoxy-delta-9-prostaglandin D2; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D037342:Pertussis Toxin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D015230:Prostaglandin D2