Effect of the pesticide, deltamethrin, on Ca2+ signaling and apoptosis in OC2 human oral cancer cells.

Abstract

Deltamethrin is a synthetic pyrethroid insecticide used extensively in pest control. Although deltamethrin has been shown to induce cytosolic free Ca(2+) concentration ([Ca(2+)]i) rises and apoptosis in different cancer cells, there is no information concerning the effects of deltamethrin on oral cancer. This study explored the effects of deltamethrin on [Ca(2+)]i and viability in OC2 human oral cancer cells. Deltamethrin, at concentrations of 5-10 μM, increased [Ca(2+)]i in a concentration-dependent manner. The Ca(2+) signal was reduced partly by removing extracellular Ca(2+). Deltamethrin-induced [Ca(2+)]i rise was not inhibited by econazole, SK&F96365, phorbol 12-myristate 13 acetate (PMA) or GF109203X, but was inhibited by nifedipine. In Ca(2+)-free medium, 10-μM deltamethrin pretreatment inhibited the [Ca(2+)]i rise induced by the endoplasmic reticulum Ca(2+) pump inhibitor, 2,5-di-tert-butylhydroquinone (BHQ). Conversely, pretreatment with BHQ inhibited deltamethrin-induced [Ca(2+)]i rise. Inhibition of inositol 1,4,5-trisphosphate formation with phospholipase C (PLC) inhibitor U73122 did not suppress deltamethrin-induced Ca(2+) release. At concentrations between 20 and 100 μM, deltamethrin killed cells in a concentration-dependent manner. The cytotoxic effect of deltamethrin was not reversed by prechelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl. Deltamethrin-induced cell death was not caused by a preceding [Ca(2+)]i rise. Annexin V/propidium iodide staining data suggest that deltamethrin (40-60 μM) induced apoptosis in a concentration-dependent manner. To conclude, in OC2 cells, deltamethrin evoked a [Ca(2+)]i rise by inducing PLC-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry by nifedipine-sensitive Ca(2+) channels. Further, deltamethrin induced Ca(2+)-independent cell death might involve apoptosis.

• Authors: Chao-Chuan Chi, Chiang-Ting Chou, Wei-Zhe Liang, Chung-Ren Jan
• Journal: Drug and chemical toxicology (Drug Chem Toxicol) Vol. 37 Issue 1 Pg. 25-31 (Jan 2014) ISSN: 1525-6014 [Electronic] United States
• PMID: 23829777 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Hydroquinones
• Indoles
• Insecticides
• Maleimides
• Nitriles
• Pyrethrins
• 2,5-di-tert-butylhydroquinone
• decamethrin
• Econazole
• Nifedipine
• bisindolylmaleimide I
• Calcium

Topics

• Annexin A5
• Apoptosis (drug effects)
• Calcium (metabolism)
• Calcium Signaling (drug effects)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Econazole
• Humans
• Hydroquinones
• Indoles
• Insecticides (pharmacology)
• Maleimides
• Mouth Neoplasms (drug therapy)
• Nifedipine
• Nitriles (pharmacology)
• Pyrethrins (pharmacology)