title: Effect of the pesticide, deltamethrin, on Ca2+ signaling and apoptosis in OC2 human oral cancer cells.
abstract: Deltamethrin is a synthetic pyrethroid insecticide used extensively in pest control. Although deltamethrin has been shown to induce cytosolic free Ca(2+) concentration ([Ca(2+)]i) rises and apoptosis in different cancer cells, there is no information concerning the effects of deltamethrin on oral cancer. This study explored the effects of deltamethrin on [Ca(2+)]i and viability in OC2 human oral cancer cells. Deltamethrin, at concentrations of 5-10 μM, increased [Ca(2+)]i in a concentration-dependent manner. The Ca(2+) signal was reduced partly by removing extracellular Ca(2+). Deltamethrin-induced [Ca(2+)]i rise was not inhibited by econazole, SK&F96365, phorbol 12-myristate 13 acetate (PMA) or GF109203X, but was inhibited by nifedipine. In Ca(2+)-free medium, 10-μM deltamethrin pretreatment inhibited the [Ca(2+)]i rise induced by the endoplasmic reticulum Ca(2+) pump inhibitor, 2,5-di-tert-butylhydroquinone (BHQ). Conversely, pretreatment with BHQ inhibited deltamethrin-induced [Ca(2+)]i rise. Inhibition of inositol 1,4,5-trisphosphate formation with phospholipase C (PLC) inhibitor U73122 did not suppress deltamethrin-induced Ca(2+) release. At concentrations between 20 and 100 μM, deltamethrin killed cells in a concentration-dependent manner. The cytotoxic effect of deltamethrin was not reversed by prechelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl. Deltamethrin-induced cell death was not caused by a preceding [Ca(2+)]i rise. Annexin V/propidium iodide staining data suggest that deltamethrin (40-60 μM) induced apoptosis in a concentration-dependent manner. To conclude, in OC2 cells, deltamethrin evoked a [Ca(2+)]i rise by inducing PLC-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry by nifedipine-sensitive Ca(2+) channels. Further, deltamethrin induced Ca(2+)-independent cell death might involve apoptosis.
authors.affiliation: Department of Otolaryngology, Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan .
authors.forename: Chao-Chuan
authors.initials: CC
authors.lastname: Chi
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Liang
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004464:Econazole; D006801:Humans; D006873:Hydroquinones; D007211:Indoles; D007306:Insecticides / Q000494:pharmacology*; D008301:Maleimides; D009062:Mouth Neoplasms / Q000188:drug therapy*; D009543:Nifedipine; D009570:Nitriles / Q000494:pharmacology*; D011722:Pyrethrins / Q000494:pharmacology*
chemical_list: D017304:Annexin A5; D006873:Hydroquinones; D007211:Indoles; D007306:Insecticides; D008301:Maleimides; D009570:Nitriles; D011722:Pyrethrins; C019359:2,5-di-tert-butylhydroquinone; C017180:decamethrin; D004464:Econazole; D009543:Nifedipine; C070515:bisindolylmaleimide I; D002118:Calcium