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- Title
Decreased Expression of Stem Cell Markers by Simvastatin in 7,12-dimethylbenz(a)anthracene (DMBA)–induced Breast Cancer.
- Authors
Rennó, André Lisboa; Alves-Júnior, Marcos José; Rocha, Rafael Malagoli; De Souza, Philipi Coutinho; de Souza, Valéria Barbosa; Jampietro, Juliano; Vassallo, José; Hyslop, Stephen; Anhê, Gabriel Forato; de Moraes Schenka, Natália Guimarães; Soares, Fernando Augusto; Schenka, André Almeida
- Abstract
Simvastatin, a competitive inhibitor of HMG-CoA reductase widely used in the treatment and prevention of hyperlipidemia-related diseases, has recently been associated to in vitro anticancer stem cell (CSC) actions. However, these effects have not been confirmed in vivo. To assess in vivo anti-CSC effects of simvastatin, female Sprague-Dawley rats with 7,12-dimethyl-benz(a)anthracene (DMBA)–induced mammary cancer and control animals were treated for 14 days with either simvastatin (20 or 40 mg/kg/day) or soybean oil (N = 60). Tumors and normal breast tissues were removed for pathologic examination and immunodetection of CSC markers. At 40 mg/kg/day, simvastatin significantly reduced tumor growth and the expression of most CSC markers. The reduction in tumor growth (80%) could not be explained solely by the decrease in CSCs, since the latter accounted for less than 10% of the neoplasia (differentiated cancer cells were also affected). Stem cells in normal, nonneoplastic breast tissues were not affected by simvastatin. Simvastatin was also associated with a significant decrease in proliferative activity but no increase in cell death. In conclusion, this is the first study to confirm simvastatin anti-CSC actions in vivo, further demonstrating that this effect is specific for neoplastic cells, but not restricted to CSCs, and most likely due to inhibition of cell proliferation.
- Subjects
CANCER stem cells; SIMVASTATIN; BREAST cancer; CELL proliferation; SPRAGUE Dawley rats
- Publication
Toxicologic Pathology, 2015, Vol 43, Issue 3, p400
- ISSN
0192-6233
- Publication type
Article
- DOI
10.1177/0192623314544707