Deltamethrin-Induced [Ca ²⁺ ] _i Rise and Death in HGB Human Glioblastoma Cells

The effect of the pesticide deltamethrin on cytosolic free Ca ²⁺ concentrations ([Ca ²⁺ ] _i ) and viability in human glioblastoma DBTRG-05MG cells is explored. [Ca ²⁺ ]i was measured in suspended cells using fura-2 as a Ca ²⁺ -sensitive fluorescent dye. Deltamethrin at concentrations of 5-60 μM increased [Ca ²⁺ ]i in a concentration-dependent fashion. The Ca ²⁺ signal was reduced partly by removing extracellular Ca ²⁺ . Deltamethrin induced Mn ²⁺ entry. Deltamethrin-induced [Ca ²⁺ ]i rise was not inhibited by nifedipine, econazole, SK&F96365, and phorbol 12-myristate 13 acetate (PMA), but was inhibited by the protein kinase C inhibitor GF109203X via blocking Ca ²⁺ release. In Ca ²⁺ -free medium, 50 μM deltamethrin pretreatment abolished the [Ca ²⁺ ] _i rise induced by the endoplasmic reticulum Ca ²⁺ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ). Conversely, pretreatment with thapsigargin/BHQ abolished deltamethrin-induced [Ca ²⁺ ] _i rise. Inhibition of inositol 1,4,5-trisphosphate formation with U73122 suppressed 50% of deltamethrin-induced [Ca ²⁺ ] _i rise. At concentrations between 10 and 80 μM 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 (BAPTA). Annexin V/propidium iodide staining data suggest that deltamethrin (10-40 μM) induced apoptosis in a concentration-dependent manner. Deltamethrin also increased levels of reactive oxygen species. Together, in human glioblastoma cells, deltamethrin induced a [Ca ²⁺ ] _i rise by inducing phospholipase C- and protein kinase C-dependent Ca ²⁺ release from the endoplasmic reticulum and Ca ²⁺ entry via non-store-operated Ca ²⁺ channels. Deltamethrin induced cell death that might involve apoptosis via mitochondrial pathways.