Effect of the pesticide, deltamethrin, on Ca2+ signaling and apoptosis in OC2 human oral cancer cells

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.