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Effects of metformin on breast cancer cell proliferation, the AMPK pathway and the cell cycle
Hadad, SM; Hardie, DG; Appleyard, V; Thompson, AM.
Afiliação
  • Hadad, SM; University of Sheffield. The Medical School. Department of Oncology. Sheffield. UK
  • Hardie, DG; University of Sheffield. The Medical School. Department of Oncology. Sheffield. UK
  • Appleyard, V; University of Sheffield. The Medical School. Department of Oncology. Sheffield. UK
  • Thompson, AM; University of Sheffield. The Medical School. Department of Oncology. Sheffield. UK
Clin. transl. oncol. (Print) ; 16(8): 746-752, ago. 2014. ilus
Artigo em Inglês | IBECS | ID: ibc-126563
Biblioteca responsável: ES1.1
Localização: BNCS
ABSTRACT

AIM:

The aim of this study was to compare the effects and mechanisms of action of metformin on estrogen receptor (ER)-positive and ER-negative breast cancer cell lines.

METHODS:

The anti-proliferative effects of metformin, and of the direct activator of adenosine monophosphate-activated protein kinase (AMPK), A-769662, on MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) breast cancer cell lines were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, a yellow tetrazole) assays. Fluorescence-activated cell sorting was also used to examine the effect of metformin on the cell cycle. Finally, phosphorylation of the metformin target AMPK, and of its potential downstream targets including acetyl-CoA carboxylase (ACC), p53, p70-S6K and Raptor, was examined using immunoblotting.

RESULTS:

Metformin and A-769662 caused significant, concentration-dependent suppression of cell proliferation with G1 cell cycle arrest in both MCF-7 and MDA-MB-231 cells. The proliferation suppression effect was more profound in MCF-7 cells. A concentration-dependent phosphorylation of AMPK was detected following metformin treatment, as was phosphorylation of ACC in both cell lines, but not p53, p70-S6k or Raptor.

CONCLUSION:

Metformin acts as a growth inhibitor in both ER-positive and ER-negative breast cancer cells in vitro, and arrests cells in G1 phase, particularly in the ER-positive MCF-7 cells. The effect is likely to be mediated by AMPK activation, in part by inhibition of fatty acid synthesis via ACC phosphorylation (AU)
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Coleções: Bases de dados nacionais / Espanha Base de dados: IBECS Assunto principal: Neoplasias da Mama / Monofosfato de Adenosina / Proteína Supressora de Tumor p53 / Antígeno Nuclear de Célula em Proliferação / Proliferação de Células / Metformina Limite: Feminino / Humanos Idioma: Inglês Revista: Clin. transl. oncol. (Print) Ano de publicação: 2014 Tipo de documento: Artigo Instituição/País de afiliação: University of Sheffield/UK
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Coleções: Bases de dados nacionais / Espanha Base de dados: IBECS Assunto principal: Neoplasias da Mama / Monofosfato de Adenosina / Proteína Supressora de Tumor p53 / Antígeno Nuclear de Célula em Proliferação / Proliferação de Células / Metformina Limite: Feminino / Humanos Idioma: Inglês Revista: Clin. transl. oncol. (Print) Ano de publicação: 2014 Tipo de documento: Artigo Instituição/País de afiliação: University of Sheffield/UK
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