The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Fluoxetine affects cytosolic cAMP, ATP, Ca2+ responses to forskolin, and survival of human ovarian granulosa tumor COV434 cells

  • Nguyen, Thi Mong Diep (Physiologie de la Reproduction & des Comportements Laboratory, Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique & Environnementale (INRAe), University of Tours) ;
  • Klett, Daniele (Physiologie de la Reproduction & des Comportements Laboratory, Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique & Environnementale (INRAe), University of Tours) ;
  • Combarnous, Yves (Physiologie de la Reproduction & des Comportements Laboratory, Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique & Environnementale (INRAe), University of Tours)
  • Received : 2020.10.05
  • Accepted : 2021.01.07
  • Published : 2021.05.01
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Abstract

Fluoxetine (FLX), a selective serotonin reuptake inhibitor antidepressant, exhibits various other mechanisms of action in numerous cell types and has been shown to induce cell death in cancer cells, paving the way for its potential use in cancer therapy. The aim of this study was to determine the off-target effects of the anti-depressant drug FLX, on the human ovarian granulosa tumor COV434 cells stimulated by forskolin (FSK), by measuring the real-time kinetics of intracellular cyclic AMP (cAMP), ATP level, cytoplasmic calcium ([Ca2+]cyt) and survival of COV434 cells. We show that incubating COV434 cells with FLX (between 0.6 and 10 μM) induces a decrease in intracellular cAMP response to FSK, a drop in ATP content and stimulates cytoplasmic Ca2+ accumulation in COV434 cells. Only the highest concentrations of FLX (5-10 μM) diminished cell viability. The present report is the first to identify an action mechanism of FLX in human tumor ovarian cells COV434 cells and thus opening the way to potential use of fluoxetine as a complementary tool, in granulosa tumor treatments.

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