The mechanism of sertraline-induced [Ca2+]i rise in human OC2 oral cancer cells.
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.
Department of Pediatrics, Ping Tung Christian Hospital, Ping Tung, Taiwan.
Jau-Min
JM
Chien
Chiang-Ting
CT
Chou
Chih-Chuan
CC
Pan
Chun-Chi
CC
Kuo
Jeng-Yu
JY
Tsai
Wei-Chuan
WC
Liao
Daih-Huang
DH
Kuo
Pochuen
P
Shieh
Chin-Man
CM
Ho
Sau-Tung
ST
Chu
Hsing-Hao
HH
Su
Cao-Chuan
CC
Chi
Chung-Ren
CR
Jan
D000928:Antidepressive Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005453:Fluorescence; D016257:Fura-2 / Q000378:metabolism; D006801:Humans; D008345:Manganese / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology*
D000928:Antidepressive Agents; D002118:Calcium; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D016257:Fura-2; D008345:Manganese; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline