4.3 Article

The mechanism of sertraline-induced [Ca2+]i rise in human OC2 oral cancer cells

Journal

HUMAN & EXPERIMENTAL TOXICOLOGY
Volume 30, Issue 10, Pages 1635-1643

Publisher

SAGE PUBLICATIONS LTD
DOI: 10.1177/0960327110396523

Keywords

Ca2+; fura-2; OC2; oral cancer; sertraline

Categories

Funding

  1. Kaohsiung Veterans General Hospital [VGHKS98-100, PS98004]

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Effect of sertraline, an antidepressant, on cytosolic free Ca2+ levels ([Ca2+](i)) in human cancer cells is unclear. This study examined if sertraline altered basal [Ca2+](i) levels in suspended 0C2 human oral cancer by using fura-2 as a Ca2+-sensitive fluorescent probe. At concentrations of 100-100 mu M, sertraline induced a [Ca2+](i) rise in a concentration-dependent fashion. The Ca2+ signal was reduced partly by removing extracellular Ca2+ indicating that Ca2+ entry and release both contributed to the [Ca2+](i) rise. Sertraline induced Mn2+ influx, leading to quench of fura-2 fluorescence suggesting Ca2+ influx. This Ca2+ influx was inhibited by suppression of phospholipase A2, inhibition of store-operated Ca2+ channels or by modulation of protein kinase C activity. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or 2,5-di-(t-butyl)-1,4-hydroquinone (BHQ) nearly abolished sertraline-induced Ca2+ release. Conversely, pretreatment with sertraline greatly reduced the inhibitor-induced [Ca2+](i) rise, suggesting that sertraline released Ca2+ from the endoplasmic reticulum. Inhibition of phospholipase C did not change sertraline-induced [Ca2+](i) rise. Together, in human oral cancer cells, sertraline induced [Ca2+](i) rises by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via store-operated Ca2+ channels.

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