Sanguinarine suppresses basal-like breast cancer growth through dihydrofolate reductase inhibition.
Biochem Pharmacol
; 90(3): 226-34, 2014 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-24875448
ABSTRACT
Basal-like breast cancer (BLBC) remains a great challenge because of its clinically aggressive nature and lack of effective targeted therapy. We analyzed the potential anti-neoplastic effects of sanguinarine, a natural benzophenanthridine alkaloid, against BLBC cells. Sanguinarine treatment resulted in a reduction of cell migration, in a dose-dependent inhibition of cell viability and in the induction of cell death by apoptosis in both human (MDA-MB-231 cells) and mouse (A17 cells) in vitro models of BLBC. In vivo experiments demonstrated that oral administration of sanguinarine reduced the development and growth of A17 transplantable tumors in FVB syngeneic mice. Western blotting analysis revealed that suppression of BLBC growth by sanguinarine was correlated with a concurrent upregulation of p27 and downregulation of cyclin D1 and with the inhibition of STAT3 activation. In addition, we identified sanguinarine as a potent inhibitor of dihydrofolate reductase (DHFR), able to impair enzyme activity even in methotrexate resistant MDA-MB-231 cells. These results provide evidence that sanguinarine is a promising anticancer drug for the treatment of BLBC.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tetra-Hidrofolato Desidrogenase
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Neoplasias da Mama
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Neoplasia de Células Basais
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Benzofenantridinas
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Antagonistas do Ácido Fólico
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Isoquinolinas
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Proteínas de Neoplasias
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Antineoplásicos Fitogênicos
Tipo de estudo:
Clinical_trials
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article