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 ([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 5-10μM, 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 Ca ²⁺-free medium, 10-μM 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 100μM, 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 (40-60μM) 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.