Effect of Fluoxetine on [Ca^(2+)]i and Cell Viability in OC2 Human Oral Cancer Cells

10.4077/CJP.2014.BAC208

Ko-Long Lin；Chiang-Ting Chou；Jin-Shiung Cheng；Hong-Tai Chang；Wei-Zhe Liang；Chun-Chi Kuo；I-Li Chen；Li-Ling Tseng；Pochuen Shieh；Ru-Fang Wu；Daih-Huang Kuo；Chung-Ren Jan

apoptosis ； Ca^(2+) ； fluoxetine ； human oral cancer cells ； OC2

The Chinese Journal of Physiology

57卷5期（2014 / 10 / 31）

256 - 264

英文

Fluoxetine is a serotonin-specific reuptake inhibitor that has been used as an antidepressant. This study examined the effect of fluoxetine on cytosolic free Ca^(2+) concentrations ([Ca^(2+)]i) and viability in OC2 human oral cancer cells. The Ca^(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca^(2+)]i, and the water soluble tetrazolium (WST-1) regent was used to measure viability. Fluoxetine-induced [Ca^(2+)]i rises concentration-dependently. The response was reduced by half by removing extracellular Ca^(2+). Fluoxetine-induced Ca^(2+) entry was enhanced by activation of protein kinase C (PKC) with phorbol 12-myristate 13 acetate (PMA) but was inhibited by inhibition of the enzyme with GF109203X. In Ca^(2+)-free medium, treatment with the endoplasmic reticulum Ca^(2+) pump inhibitor 2,5-di-tertbutylhydroquinone (BHQ) or thapsigargin abolished fluoxetine-evoked [Ca^(2+)]i rise. Conversely, treatment with fluoxetine inhibited BHQ/thapsigargin-evoked [Ca^(2+)]i rise. Inhibition of phospholipase C (PLC) with U73122 abolished fluoxetine-induced [Ca^(2+)]i rise. At 20-80 μM, fluoxetine decreased cell viability concentration-dependently, which was not altered by chelating cytosolic Ca^(2+) with 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). At 20-60 μM, fluoxetine induced apoptosis as detected by annexin V/propidium iodide (PI) staining. Together, in OC2 cells, fluoxetine induced [Ca^(2+)]i rises by evoking PLC-dependent Ca^(2+) release from the endoplasmic reticulum and Ca^(2+) entry via PKC-regulated mechanisms. Fluoxetine also caused Ca^(2+)-independent apoptosis.

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