Deltamethrin-Induced [Ca2+]i Rise and Death in HGB Human Glioblastoma Cells

The effect of the pesticide deltamethrin on cytosolic free Ca2+ concentrations ([Ca2+](i)) and viability in human glioblastoma DBTRG-05MG cells is explored. [Ca2+](i) was measured in suspended cells using fura-2 as a Ca2+-sensitive fluorescent dye. Deltamethrin at concentrations of 5-60 mu M increased [Ca2+](i) in a concentration-dependent fashion. The Ca2+ signal was reduced partly by removing extracellular Ca2+. Deltamethrin induced Mn2+ entry leading to quenching of fura-2 fluorescence. Deltamethrin-induced [Ca2+](i) rise was not inhibited by nifedipine, econazole, SK&F96365, and phorbol 12-myristate 13 acetate, but was inhibited by the protein kinase C (PKC) inhibitor GF109203X via blocking Ca2+ release. In Ca2+-free medium, 50 mu M deltamethrin pretreatment abolished the [Ca2+](i) rise induced by the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (TG) or 2,5-di-tert-butylhydroquinone (BHQ). Conversely, pretreatment with TG/BHQ abolished deltamethrin-induced [Ca2+](i) rise. Inhibition of inositol 1,4,5-trisphosphate formation with U73122 suppressed 50% of deltamethrin-induced [Ca2+](i) rise. At concentrations between 10 and 80 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 (BAPTA). Annexin V/propidium iodide staining data suggest that deltamethrin (10-40 mu M) induced apoptosis in a concentration-dependent manner. Deltamethrin also increased levels of reactive oxygen species. Together, in human glioblastoma cells, deltamethrin induced a [Ca2+](i) rise by inducing phospholipase C- and PKC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via non-store-operated Ca2+ channels. Deltamethrin induced cell death that might involve apoptosis via mitochondrial pathways.