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Lin K.-L.,Kaohsiung Veterans General Hospital | Chou C.-T.,Chang Gung University | Cheng J.-S.,Kaohsiung Veterans General Hospital | Chang H.-T.,Kaohsiung Veterans General Hospital | And 8 more authors.
Chinese Journal of Physiology | Year: 2014

Fluoxetine is a serotonin-specific reuptake inhibitor that has been used as an antidepressant. This study examined the effect of fluoxetine on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability in OC2 human oral cancer cells. The Ca2+-sensitive fluorescent dye fura-2 was used to measure [Ca2+]i, and the water soluble tetrazolium (WST-1) regent was used to measure viability. Fluoxetine-induced [Ca2+]i rises concentration-dependently. The response was reduced by half by removing extracellular Ca2+. Fluoxetine-induced Ca2+ 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 Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tertbutylhydroquinone (BHQ) or thapsigargin abolished fluoxetine-evoked [Ca2+]i rise. Conversely, treatment with fluoxetine inhibited BHQ/thapsigargin-evoked [Ca2+]i rise. Inhibition of phospholipase C (PLC) with U73122 abolished fluoxetine-induced [Ca2+]i rise. At 20-80 μM, fluoxetine decreased cell viability concentration-dependently, which was not altered by chelating cytosolic Ca2+ 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 [Ca2+]i rises by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-regulated mechanisms. Fluoxetine also caused Ca2+-independent apoptosis. © 2014 by The Chinese Physiological Society and Airiti Press Inc.

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