title: Deltamethrin-Induced [Ca ²⁺ ]i Rise and Death in HGB Human Glioblastoma Cells.
abstract: The effect of the pesticide deltamethrin on cytosolic free Ca ²⁺ 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 μM increased [Ca²⁺]i in a concentration-dependent fashion.  The Ca²⁺ signal was reduced partly by removing extracellular Ca ²⁺ .  Deltamethrin induced Mn ²⁺ entry leading to quenching of fura-2 fluorescence. Deltamethrin-induced [Ca²⁺ ]i rise was not inhibited by nifedipine, econazole, SKF96365, 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 μM deltamethrin pretreatment abolished the [Ca²⁺]i rise induced by the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin (TG) or 2,5-di-tertbutylhydroquinone (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 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 concentrationdependent 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.
authors.affiliation: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.
authors.forename: Shu-Shong
authors.initials: SS
authors.lastname: Hsu
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005909:Glioblastoma; D006801:Humans; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D010738:Type C Phospholipases; D002118:Calcium