Effect of fluoxetine on [Ca 2+ ]i and cell viability in OC2 human oral cancer cells

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

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

9 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)256-264
Number of pages9
JournalChinese Journal of Physiology
Volume57
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 by The Chinese Physiological Society and Airiti Press Inc.

Keywords

  • Apoptosis
  • Ca
  • Fluoxetine
  • Human oral cancer cells
  • OC2

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