Paroxetine-induced Ca 2+ movement and death in OC2 human oral cancer cells

Yi Chien Fang, Chiang Ting Chou, Chih Chuan Pan, Yao Dung Hsieh, Wei Zhe Liang, David Chao, Jeng Yu Tsai, Wei Chuan Liao, Daih Huang Kuo, Pochuen Shieh, Chun Chi Kuo, Chung Ren Jan, Chen Fu Shaw*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

24 Scopus citations

Abstract

The effect of the antidepressant paroxetine on cytosolic free Ca 2+ concentrations ([Ca 2+ ] i ) in OC2 human oral cancer cells is unclear. This study explored whether paroxetine changed basal [Ca 2+ ] i levels in suspended OC2 cells by using fura-2 as a Ca 2+ -sensitive fluorescent dye. Paroxetine at concentrations between 100-1,000 μM increased [Ca 2+ ] i in a concentration-dependent manner. The Ca 2+ signal was reduced by 50% by removing extracellular Ca 2+ . Paroxetine-induced Ca 2+ influx was inhibited by the store-operated Ca 2+ channel blockers nifedipine, econazole and SK&F96365, and protein kinase C modulators. In Ca 2+ -free medium, pretreatment with the endoplasmic reticulum Ca 2+ pump inhibitor thapsigargin abolished paroxetine-induced [Ca 2+ ] i rise. Inhibition of phospholipase C with U73122 did not alter paroxetine-induced [Ca 2+ ] i rise. Paroxetine at 10-50 μM induced cell death in a concentrationdependent manner. The death was not reversed when cytosolic Ca 2+ was chelated with 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Propidium iodide staining suggests that apoptosis plays a role in the death. Collectively, in OC2 cells, paroxetine induced [Ca 2+ ] i rise by causing phospholipase C-independent Ca 2+ release from the endoplasmic reticulum and Ca 2+ influx via storeoperated Ca 2+ channels in a manner regulated by protein kinase C and phospholipase A2. Paroxetine (up to 50 μM) induced cell death in a Ca 2+ -independent manner.

Original languageEnglish
Pages (from-to)310-317
Number of pages8
JournalChinese Journal of Physiology
Volume54
Issue number5
DOIs
StatePublished - 2011
Externally publishedYes

Keywords

  • OC2
  • Oral cancer
  • Paroxetine

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