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

Abstract

<jats:p> Bifenthrin, a commonly used pyrethroid pesticide, evokes various toxicological effects in different models. However, the effect of bifenthrin on cytosolic-free Ca<jats:sup>2+</jats:sup> level ([Ca<jats:sup>2+</jats:sup>] <jats:sub>i</jats:sub>) and cytotoxicity in human prostate cancer cells is unclear. This study examined whether bifenthrin altered Ca<jats:sup>2+</jats:sup> homeostasis and cell viability in PC3 human prostate cancer cells. [Ca<jats:sup>2+</jats:sup>] <jats:sub>i</jats:sub> in suspended cells were measured using the fluorescent Ca<jats:sup>2+</jats:sup>-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 [Ca<jats:sup>2+</jats:sup>] <jats:sub>i</jats:sub> rises. Ca<jats:sup>2+</jats:sup> removal reduced the signal by approximately 30%. In Ca<jats:sup>2+</jats:sup>-free medium, treatment with the endoplasmic reticulum Ca<jats:sup>2+</jats:sup> pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished bifenthrin-evoked [Ca<jats:sup>2+</jats:sup>] <jats:sub>i</jats:sub> rises. Conversely, treatment with bifenthrin abolished BHQ-evoked [Ca<jats:sup>2+</jats:sup>] <jats:sub>i</jats:sub> rises. Inhibition of phospholipase C (PLC) with U73122 significantly inhibited bifenthrin-induced [Ca<jats:sup>2+</jats:sup>] <jats:sub>i</jats:sub> rises. Mn<jats:sup>2+</jats:sup> has been shown to enter cells through similar mechanisms as Ca<jats:sup>2+</jats:sup> but quenches fura-2 fluorescence at all excitation wavelengths. Bifenthrin (400 μM)-induced Mn<jats:sup>2+</jats:sup> influx implicates that Ca<jats:sup>2+</jats:sup> entry occurred. Bifenthrin-induced Ca<jats:sup>2+</jats:sup> 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 Ca<jats:sup>2+</jats:sup> channels: nifedipine, econazole, and SKF96365. Bifenthrin at 175–275 μM decreased cell viability, which was not reversed by pretreatment with the Ca<jats:sup>2+</jats:sup> chelator 1,2-bis(2-aminophenoxy) ethane- N, N, N′, N′-tetra acetic acid-acetoxymethyl ester. Together, in PC3 cells, bifenthrin-induced [Ca<jats:sup>2+</jats:sup>] <jats:sub>i</jats:sub> rises by evoking PLC-dependent Ca<jats:sup>2+</jats:sup> release from the endoplasmic reticulum and Ca<jats:sup>2+</jats:sup> entry via PKC-sensitive store-operated Ca<jats:sup>2+</jats:sup> entry. Bifenthrin also caused Ca<jats:sup>2+</jats:sup>-independent cell death. </jats:p>

Insight Into Microbial Applications for the Biodegradation of Pyrethroid Insecticides

“…Antiandrogenic activity of cyfluthrin and β-cyfluthrin in a carcinogenic cell line MDA-kb2 has also been reported (Zhang et al, 2008). Bifenthrin evokes various toxicological effects in different human cells by modifying homeostasis and cell viability in human prostate cancer cells (Chien et al, 2019). Bifenthrin acts as endocrine disrupting chemical by inhibiting the expression of glucocorticoid and estrogen receptor (Ligocki et al, 2019).…”