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 Ca2+ concentration ([Ca2+](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 [Ca2+](i) and viability in OC2 human oral cancer cells. Deltamethrin, at concentrations of 5-10 mu M, increased [Ca2+](i) in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. Deltamethrin-induced [Ca2+](i) rise was not inhibited by econazole, SK&F96365, phorbol 12-myristate 13 acetate (PMA) or GF109203X, but was inhibited by nifedipine. In Ca2+-free medium, 10-mu M deltamethrin pretreatment inhibited the [Ca2+](i) rise induced by the endoplasmic reticulum Ca2+ pump inhibitor, 2,5-di-tert-butylhydroquinone (BHQ). Conversely, pretreatment with BHQ inhibited deltamethrin-induced [Ca2+](i) rise. Inhibition of inositol 1,4,5-trisphosphate formation with phospholipase C (PLC) inhibitor U73122 did not suppress deltamethrin-induced Ca2+ release. At concentrations between 20 and 100 mu M, deltamethrin killed cells in a concentration-dependent manner. The cytotoxic effect of deltamethrin was not reversed by prechelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl. Deltamethrin-induced cell death was not caused by a preceding [Ca2+](i) rise. Annexin V/propidium iodide staining data suggest that deltamethrin (40-60 mu M) induced apoptosis in a concentration-dependent manner. To conclude, in OC2 cells, deltamethrin evoked a [Ca2+](i) rise by inducing PLC-independent Ca2+ release from the endoplasmic reticulum and Ca2+ entry by nifedipine-sensitive Ca2+ channels. Further, deltamethrin induced Ca2+-independent cell death might involve apoptosis.