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Type: Artigo de periódico
Title: Decreased Expression Of Stem Cell Markers By Simvastatin In 7,12-dimethylbenz(a)anthracene (dmba)-induced Breast Cancer
Author: Renno
Andre Lisboa; Alves-Junior
Marcos Jose; Rocha
Rafael Malagoli; De Souza
Philipi Coutinho; de Souza
Valeria Barbosa; Jampietro
Juliano; Vassallo
Jose; Hyslop
Stephen; Anhe
Gabriel Forato; de Moraes Schenka
Natalia Guimaraes; Soares
Fernando Augusto; Schenka
Andre 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.
Subject: Therapeutic Implications
Mammary Carcinogenesis
Rights: embargo
Identifier DOI: 10.1177/0192623314544707
Date Issue: 2015
Appears in Collections:Unicamp - Artigos e Outros Documentos

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