PloS one, 2012-11, Vol.7 (11), p.e50043
2012
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- Autor(en) / Beteiligte
- Titel
- Antiproliferative effects of fluoxetine on colon cancer cells and in a colonic carcinogen mouse model
- Ist Teil von
- PloS one, 2012-11, Vol.7 (11), p.e50043
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The antidepressant fluoxetine has been under discussion because of its potential influence on cancer risk. It was found to inhibit the development of carcinogen-induced preneoplastic lesions in colon tissue, but the mechanisms of action are not well understood. Therefore, we investigated anti-proliferative effects, and used HT29 colon tumor cells in vitro, as well as C57BL/6 mice exposed to intra-rectal treatment with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as models. Fluoxetine increased the percentage of HT29 cells in the G(0)/G(1) phase of cell-cycle, and the expression of p27 protein. This was not related to an induction of apoptosis, reactive oxygen species or DNA damage. In vivo, fluoxetine reduced the development of MNNG-induced dysplasia and vascularization-related dysplasia in colon tissue, which was analyzed by histopathological techniques. An anti-proliferative potential of fluoxetine was observed in epithelial and stromal areas. It was accompanied by a reduction of VEGF expression and of the number of cells with angiogenic potential, such as CD133, CD34, and CD31-positive cell clusters. Taken together, our findings suggest that fluoxetine treatment targets steps of early colon carcinogenesis. This confirms its protective potential, explaining at least partially the lower colon cancer risk under antidepressant therapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0050043Titel-ID: cdi_plos_journals_1350901604
- Format
- –
- Schlagworte
- Analysis, Angiogenesis, Animal models, Animals, Anticarcinogenic Agents - pharmacology, Antiproliferatives, Apoptosis, Apoptosis - drug effects, Biology, Cancer, Cancer therapies, Carcinogenesis, Carcinogens, Carcinogens - pharmacology, CD34 antigen, Cell cycle, Cell Cycle - drug effects, Cell Proliferation - drug effects, Cell Transformation, Neoplastic - drug effects, Colon, Colon cancer, Colonic Neoplasms - chemically induced, Colonic Neoplasms - drug therapy, Colonic Neoplasms - metabolism, Colorectal cancer, Cyclin-Dependent Kinase Inhibitor p27 - metabolism, Deoxyribonucleic acid, DNA, DNA damage, DNA Damage - drug effects, Dysplasia, Experiments, Female, Flow cytometry, Fluoxetine, Fluoxetine - pharmacology, G1 phase, Gastrointestinal diseases, Gene expression, Health aspects, Health risks, HT29 Cells, Humans, Hydrogen peroxide, Kinases, Lesions, Medical schools, Medicine, Mice, Oxygen, Proteins, Reactive oxygen species, Reactive Oxygen Species - metabolism, Rectum, Stem cells, Toxicology, Tumor cells, Vascular endothelial growth factor, Vascularization