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 language | English |
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Pages (from-to) | 310-317 |
Number of pages | 8 |
Journal | Chinese Journal of Physiology |
Volume | 54 |
Issue number | 5 |
DOIs | |
State | Published - 2011 |
Externally published | Yes |
Keywords
- OC2
- Oral cancer
- Paroxetine