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Effect of Methoxychlor on Ca 2+ Handling and Viability in OC2 Human Oral Cancer Cells
Author(s) -
Tseng LiLing,
Shu SuShung,
Kuo ChunChi,
Chou ChiangTing,
Hsieh YaoDung,
Chu SauTung,
Chi ChaoChuan,
Liang WeiZhe,
Ho ChinMan,
Jan ChungRen
Publication year - 2011
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2010.00662.x
Subject(s) - methoxychlor , thapsigargin , phospholipase c , chemistry , endoplasmic reticulum , phospholipase a2 , medicine , endocrinology , biology , microbiology and biotechnology , biochemistry , signal transduction , enzyme , pesticide , agronomy
The effect of the insecticide methoxychlor on the physiology of oral cells is unknown. This study aimed to explore the effect of methoxychlor on cytosolic Ca 2+ concentrations ([Ca 2+ ] i ) in human oral cancer cells (OC2) by using the Ca 2+ ‐sensitive fluorescent dye fura‐2. Methoxychlor at 5–20 μM increased [Ca 2+ ] i in a concentration‐dependent manner. The signal was reduced by 70% by removing extracellular Ca 2+ . Methoxychlor‐induced Ca 2+ entry was not affected by nifedipine, econazole, SK&F96365 and protein kinase C modulators but was inhibited by the phospholipase A2 inhibitor aristolochic acid. In Ca 2+ ‐free medium, treatment with the endoplasmic reticulum Ca 2+ pump inhibitor thapsigargin or 2,5‐di‐tert‐butylhydroquinone (BHQ) inhibited or abolished methoxychlor‐induced [Ca 2+ ] i rise. Incubation with methoxychlor also inhibited thapsigargin‐ or BHQ‐induced [Ca 2+ ] i rise. Inhibition of phospholipase C with U73122 did not alter methoxychlor‐induced [Ca 2+ ] i rise. At 5–20 μM, methoxychlor killed cells in a concentration‐dependent manner. The cytotoxic effect of methoxychlor was not reversed by chelating cytosolic Ca 2+ with 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N’,N’‐tetraacetic acid/AM (BAPTA/AM). Annexin V‐FITC data suggest that methoxychlor (10 and 20 μM) evoked apoptosis in a concentration‐dependent manner. Together, in human OC2, methoxychlor induced a [Ca 2+ ] i rise probably by inducing phospholipase C‐independent Ca 2+ release from the endoplasmic reticulum and Ca 2+ entry via phospholipase A 2 ‐sensitive channels. Methoxychlor induced cell death that may involve apoptosis.