Fluoxetine inhibits the extracellular signal regulated kinase pathway and suppresses growth of cancer cells

Fluoxetine (FLX) is a widely prescribed antidepressant. Concerns were raised about the potential impact of FLX on cancer growth, because FLX was shown to promote development of breast cancer in rodents. Here we studied the effect of FLX on tumor growth in lung (A549), colon (HT29), neuroblastoma (SK...

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Bibliographic Details
Published in:Cancer biology & therapy 2008-10, Vol.7 (10), p.1685-1693
Main Authors: Stepulak, Andrzej, Rzeski, Wojciech, Sifringer, Marco, Brocke, Katja, Gratopp, Alexander, Kupisz, Krzysztof, Turski, Lechoslaw, Ikonomidou, Chrysanthy
Format: Article
Language:English
Subjects:
Antidepressive Agents - pharmacology
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cell Cycle - drug effects
Cell Cycle Proteins - metabolism
Cell Line, Tumor
Cell Proliferation
Cell Survival
Cycle
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Extracellular Signal-Regulated MAP Kinases - metabolism
Flow Cytometry - methods
Fluoxetine - pharmacology
Humans
Landes
Organogenesis
Phosphorylation
Proteins
Receptors, Serotonin - drug effects
Serotonin - metabolism
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Summary:Fluoxetine (FLX) is a widely prescribed antidepressant. Concerns were raised about the potential impact of FLX on cancer growth, because FLX was shown to promote development of breast cancer in rodents. Here we studied the effect of FLX on tumor growth in lung (A549), colon (HT29), neuroblastoma (SKNAS), medulloblastoma/rhabdomyosarcoma (TE671), astrocytoma (MOGGCCM) and breast (T47D) cancer cells and explored potential mechanisms of its action. In our study, FLX reduced growth of cancer cells in vitro in a concentration dependent manner. The antiproliferative effect of FLX was already evident after 24 hrs exposure and more pronounced at 96 hrs. We demonstrate that FLX inhibits phosphorylation of ERK1/2 kinases in a time and concentration-dependent manner, followed by reduced phosphorylation of transcription factor c-Myc in A549 and HT29 cells. After treatment with FLX, A549 and HT29 cells demonstrated concentration-dependent decrease in the expression of c-fos, c-jun, cyclin A, cyclin D1, and increased expression of p21waf1 and p53 genes, which resulted in slowing of the cell cycle progression. We suggest that these changes could be responsible for observed inhibition of cancer cell proliferation during FLX treatment in vitro.
ISSN:1538-4047
1555-8576
DOI:10.4161/cbt.7.10.6664