Ca2+ movement and cytotoxicity induced by the pyrethroid pesticide bifenthrin in human prostate cancer cells

J. M. Chien, W. Z. Liang, W. C. Liao, C. C. Kuo, C. T. Chou, L. J. Hao, C. R. Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

5 Scopus citations

Abstract

Bifenthrin, a commonly used pyrethroid pesticide, evokes various toxicological effects in different models. However, the effect of bifenthrin on cytosolic-free Ca2+ level ([Ca2+] i) and cytotoxicity in human prostate cancer cells is unclear. This study examined whether bifenthrin altered Ca2+ homeostasis and cell viability in PC3 human prostate cancer cells. [Ca2+] i in suspended cells were measured using the fluorescent Ca2+-sensitive dye fura-2. Cell viability was examined by 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 assay. Bifenthrin (100–400 μM) concentration-dependently induced [Ca2+] i rises. Ca2+ removal reduced the signal by approximately 30%. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished bifenthrin-evoked [Ca2+] i rises. Conversely, treatment with bifenthrin abolished BHQ-evoked [Ca2+] i rises. Inhibition of phospholipase C (PLC) with U73122 significantly inhibited bifenthrin-induced [Ca2+] i rises. Mn2+ has been shown to enter cells through similar mechanisms as Ca2+ but quenches fura-2 fluorescence at all excitation wavelengths. Bifenthrin (400 μM)-induced Mn2+ influx implicates that Ca2+ entry occurred. Bifenthrin-induced Ca2+ entry was inhibited by 30% by protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate) and inhibitor (GF109203X) and three inhibitors of store-operated Ca2+ channels: nifedipine, econazole, and SKF96365. Bifenthrin at 175–275 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N′,N′-tetra acetic acid-acetoxymethyl ester. Together, in PC3 cells, bifenthrin-induced [Ca2+] i rises by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Bifenthrin also caused Ca2+-independent cell death.

Original languageEnglish
Pages (from-to)1145-1154
Number of pages10
JournalHuman and Experimental Toxicology
Volume38
Issue number10
DOIs
StatePublished - 01 10 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author(s) 2019.

Keywords

  • Bifenthrin
  • Ca
  • cytotoxicity
  • endoplasmic reticulum
  • prostate cancer cells

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