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- Title
The mechanism of sertraline-induced [Ca2+]i rise in human OC2 oral cancer cells.
- Authors
Chien, Jau-Min; Chou, Chiang-Ting; Pan, Chih-Chuan; Kuo, Chun-Chi; Tsai, Jeng-Yu; Liao, Wei-Chuan; Kuo, Daih-Huang; Shieh, Pochuen; Ho, Chin-Man; Chu, Sau-Tung; Su, Hsing-Hao; Chi, Cao-Chuan; Jan, Chung-Ren
- Abstract
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 OC2 human oral cancer by using fura-2 as a Ca2+-sensitive fluorescent probe. At concentrations of 10−100 μM, 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.
- Subjects
SERTRALINE; CANCER cells; ANTIDEPRESSANTS; CALCIUM channels; PHOSPHOLIPASE A2; HYDROQUINONE
- Publication
Human & Experimental Toxicology, 2011, Vol 30, Issue 10, p1635
- ISSN
0960-3271
- Publication type
Article
- DOI
10.1177/0960327110396523