In:
Human & Experimental Toxicology, SAGE Publications, Vol. 30, No. 10 ( 2011-10), p. 1635-1643
Abstract:
Effect of sertraline, an antidepressant, on cytosolic free Ca 2+ levels ([Ca 2+ ] i ) in human cancer cells is unclear. This study examined if sertraline altered basal [Ca 2+ ] i levels in suspended OC2 human oral cancer by using fura-2 as a Ca 2+ -sensitive fluorescent probe. At concentrations of 10−100 μM, sertraline induced a [Ca 2+ ] i rise in a concentration-dependent fashion. The Ca 2+ signal was reduced partly by removing extracellular Ca 2+ indicating that Ca 2+ entry and release both contributed to the [Ca 2+ ] i rise. Sertraline induced Mn 2+ influx, leading to quench of fura-2 fluorescence suggesting Ca 2+ influx. This Ca 2+ influx was inhibited by suppression of phospholipase A2, inhibition of store-operated Ca 2+ channels or by modulation of protein kinase C activity. In Ca 2+ -free medium, pretreatment with the endoplasmic reticulum Ca 2+ pump inhibitor thapsigargin or 2,5-di-(t-butyl)-1,4-hydroquinone (BHQ) nearly abolished sertraline-induced Ca 2+ release. Conversely, pretreatment with sertraline greatly reduced the inhibitor-induced [Ca 2+ ] i rise, suggesting that sertraline released Ca 2+ from the endoplasmic reticulum. Inhibition of phospholipase C did not change sertraline-induced [Ca 2+ ] i rise. Together, in human oral cancer cells, sertraline induced [Ca 2+ ] i rises by causing phospholipase C-independent Ca 2+ release from the endoplasmic reticulum and Ca 2+ influx via store-operated Ca 2+ channels.
Type of Medium:
Online Resource
ISSN:
0960-3271
,
1477-0903
DOI:
10.1177/0960327110396523
Language:
English
Publisher:
SAGE Publications
Publication Date:
2011
detail.hit.zdb_id:
1483723-7
