Non-specific effects of leukotriene synthesis inhibitors on HeLa cell physiology.
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.
Sabirsh
Alan
A
Division of Physiological Chemistry II, Department of Medical Biochemistry, Biophysics, Karolinska Institute, Sweden. Alan.Sabirsch@ki.se
Bristulf
Jesper
J
Karlsson
Ulf
U
Owman
Christer
C
Haeggström
Jesper Z
JZ
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
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