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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	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
Description	Country affiliation: Taiwan Author Affiliation: Chien JM ( Department of Pediatrics, Ping Tung Christian Hospital, Ping Tung, Taiwan.)
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.
File Format	HTM / HTML
ISSN	09603271
Issue Number	10
Volume Number	30
e-ISSN	14770903
Journal	Human & Experimental Toxicology
Language	English
Publisher	Sage Publication
Publisher Date	2011-10-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Toxicology Antidepressive Agents Pharmacology Calcium Metabolism Serotonin Uptake Inhibitors Sertraline Calcium Channel Blockers Cell Line, Tumor Enzyme Inhibitors Fluorescence Fura-2 Humans Manganese Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Medicine Toxicology

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