PMID- 32314600 OWN - NLM STAT- MEDLINE DCOM- 20210316 LR - 20210316 IS - 1477-0903 (Electronic) IS - 0960-3271 (Linking) VI - 39 IP - 9 DP - 2020 Sep TI - Action of the insecticide cyfluthrin on Ca(2+) signal transduction and cytotoxicity in human osteosarcoma cells. PG - 1268-1276 LID - 10.1177/0960327120918298 [doi] AB - Cyfluthrin is a pyrethroid insecticide and common household pesticide. The effect of cyfluthrin on Ca(2+)-related physiology in human osteosarcoma is unclear. This study investigated the effect of cyfluthrin on cytosolic-free Ca(2+) concentrations ([Ca(2+)](i)) and viability in MG63 human osteosarcoma cells. Cyfluthrin concentration-dependently induced [Ca(2+)](i) rises. Cyfluthrin-induced Ca(2+) entry was confirmed by the Mn(2+)-induced quench of fura-2 fluorescence. Cyfluthrin at concentrations of 10-100 muM induced [Ca(2+)](i) rises. Ca(2+) removal reduced the signal by approximately 50%. Cyfluthrin (100 muM) induced Mn(2+) influx suggesting Ca(2+) entry. Cyfluthrin-induced Ca(2+) 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 Ca(2+) channels: nifedipine, econazole, and SKF96365. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) completely inhibited cyfluthrin-evoked [Ca(2+)](i) rises. Conversely, treatment with cyfluthrin abolished TG-evoked [Ca(2+)](i) rises. Inhibition of phospholipase C (PLC) with 1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dion abolished cyfluthrin-induced [Ca(2+)](i) rises. Cyfluthrin at 25-65 muM decreased cell viability, which was not reversed by pretreatment with the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. Together, in MG63 cells, cyfluthrin induced [Ca(2+)](i) rises by evoking PLC-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via PKC-sensitive store-operated Ca(2+) entry. Cyfluthrin also caused Ca(2+)-independent cell death. FAU - Lu, Y-C AU - Lu YC AD - Department of Orthopedics, Kaohsiung Veterans General Hospital, Kaohsiung. FAU - Liang, W-Z AU - Liang WZ AD - Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung. AD - Department of Pharmacy, Tajen University, Pingtung. FAU - Kuo, C-C AU - Kuo CC AD - Department of Nursing, Tzu Hui Institute of Technology, Pingtung. FAU - Hao, L-J AU - Hao LJ AD - Department of Endocrinology and Metabolism, Kaohsiung Veterans General Hospital Tainan Branch, Tainan. AD - Chung Hwa University of Medical and Technology, Tainan. FAU - Chou, C-T AU - Chou CT AD - Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chiayi Campus, Puzi City, Chiayi County. AD - Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital Chiayi Branch, Puzi City, Chiayi County. FAU - Jan, C-R AU - Jan CR AUID- ORCID: 0000-0003-4570-4709 AD - Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung. LA - eng PT - Journal Article DEP - 20200421 PL - England TA - Hum Exp Toxicol JT - Human & experimental toxicology JID - 9004560 RN - 0 (Insecticides) RN - 0 (Nitriles) RN - 0 (Pyrethrins) RN - EC 3.1.4.- (Type C Phospholipases) RN - SCM2QLZ6S0 (cyfluthrin) RN - SY7Q814VUP (Calcium) SB - IM MH - Calcium/analysis MH - Calcium Signaling/*drug effects MH - Cell Death/drug effects MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Humans MH - Insecticides/*toxicity MH - Nitriles/*toxicity MH - Osteosarcoma MH - Pyrethrins/*toxicity MH - Type C Phospholipases/metabolism OTO - NOTNLM OT - Ca2+ OT - cyfluthrin OT - endoplasmic reticulum OT - human osteosarcoma cells OT - phospholipase C EDAT- 2020/04/22 06:00 MHDA- 2021/03/17 06:00 CRDT- 2020/04/22 06:00 PHST- 2020/04/22 06:00 [pubmed] PHST- 2021/03/17 06:00 [medline] PHST- 2020/04/22 06:00 [entrez] AID - 10.1177/0960327120918298 [doi] PST - ppublish SO - Hum Exp Toxicol. 2020 Sep;39(9):1268-1276. doi: 10.1177/0960327120918298. Epub 2020 Apr 21.