Action of the insecticide cyfluthrin on Ca2+ signal transduction and cytotoxicity in human osteosarcoma cells

• Published in: Human & experimental toxicology 2020-09, Vol.39 (9), p.1268-1276
• Main Authors: Lu, Y-C, Liang, W-Z, Kuo, C-C, Hao, L-J, Chou, C-T, Jan, C-R
• Format: Article
• Language: English
• Subjects: Acetic acid; Biomedical materials; Bone cancer; Ca2-transporting ATPase; Calcium (intracellular); Calcium (reticular); Calcium channels; Calcium influx; Calcium ions; Calcium signalling; Cell death; Cell viability; Cytotoxicity; Econazole; Endoplasmic reticulum; Ethane; Fluorescence; Fura-2; Insecticides; Kinases; Nifedipine; Osteosarcoma; Osteosarcoma cells; Pesticides; Phorbol 12-myristate 13-acetate; Phospholipase; Phospholipase C; Pretreatment; Protein kinase C; Sarcoma; Signal transduction; Thapsigargin; Toxicity
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327120918298

Cyfluthrin is a pyrethroid insecticide and common household pesticide. The effect of cyfluthrin on Ca2+-related physiology in human osteosarcoma is unclear. This study investigated the effect of cyfluthrin on cytosolic-free Ca2+ concentrations ([Ca2+]i) and viability in MG63 human osteosarcoma cells. Cyfluthrin concentration-dependently induced [Ca2+]i rises. Cyfluthrin-induced Ca2+ entry was confirmed by the Mn2+-induced quench of fura-2 fluorescence. Cyfluthrin at concentrations of 10–100 μM induced [Ca2+]i rises. Ca2+ removal reduced the signal by approximately 50%. Cyfluthrin (100 μM) induced Mn2+ influx suggesting Ca2+ entry. Cyfluthrin-induced Ca2+ entry was inhibited 50% by protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate) and inhibitor (GF109203X) and also by three inhibitors of store-operated Ca2+ channels: nifedipine, econazole, and SKF96365. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (TG) completely inhibited cyfluthrin-evoked [Ca2+]i rises. Conversely, treatment with cyfluthrin abolished TG-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with 1-[6-[((17β)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dion abolished cyfluthrin-induced [Ca2+]i rises. Cyfluthrin at 25–65 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid–acetoxymethyl ester. Together, in MG63 cells, cyfluthrin induced [Ca2+]i rises by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Cyfluthrin also caused Ca2+-independent cell death.