title: Non-specific effects of leukotriene synthesis inhibitors on HeLa cell physiology.
abstract: We examined the effects of various leukotriene synthesis inhibitors on calcium signalling in HeLa cells, before and after transfection with BLT(1). All of the inhibitors studied were found to reduce increases in intracellular calcium concentration induced by BLT(1), but also by an ionophore or activation of various G-protein coupled receptors, regardless of BLT(1) expression. In order to explore the mechanism of these apparently general effects we examined HeLa cell expression of leukotriene receptors and biosynthetic enzymes and found that the genes for key leukotriene synthesis enzymes and all of the leukotriene receptors were not expressed. Leukotrienes are involved in the pathology of a variety of cancers, and for HeLa cells leukotrienes have been reported to be important for aspects of the carcinogenic phenotype. We find that leukotriene synthesis inhibitors have non-specific effects, so careful controls are necessary to avoid interpreting non-specific effects as evidence for leukotriene involvement.
authors.affiliation: Division of Physiological Chemistry II, Department of Medical Biochemistry, Biophysics, Karolinska Institute, Sweden. Alan.Sabirsch@ki.se
authors.forename: Alan
authors.initials: A
authors.lastname: Sabirsh
authors.forename: Jesper
authors.initials: J
authors.lastname: Bristulf
authors.forename: Ulf
authors.initials: U
authors.lastname: Karlsson
authors.forename: Christer
authors.initials: C
authors.lastname: Owman
authors.forename: Jesper Z
authors.initials: JZ
authors.lastname: Haeggström
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000179:Acrylates / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis; D001095:Arachidonic Acids / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007962:Leukocytes / Q000201:enzymology; D020024:Leukotriene Antagonists / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis; D063065:Organophosphonates / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D018102:Receptors, Leukotriene B4 / Q000235:genetics / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014162:Transfection; D002722:Chlorobenzenes
chemical_list: D000085:Acetates; D000179:Acrylates; D001094:Arachidonate 5-Lipoxygenase; D001095:Arachidonic Acids; D001565:Benzoates; D007211:Indoles; D015759:Ionomycin; D020024:Leukotriene Antagonists; D007975:Leukotriene B4; D063065:Organophosphonates; D018102:Receptors, Leukotriene B4; D019284:Thapsigargin; D013876:Thiophenes; C507385:2-(thienyl)ethyl-3,4-dihydroxybenzylidenecyanoacetic acid; C104810:methyl arachidonylfluorophosphonate; C060893:MK-886; D002722:Chlorobenzenes; C069438:3-(4-octadecyl)benzoylacrylic acid