Effects on Cell Viability and on Apoptosis in Tumoral (MCF-7) and in Normal (MCF10A) Epithelial Breast Cells after Human Chorionic Gonadotropin and Derivated-Angiotensin Peptides Treatments

Silvana Aparecida Alves Corrêa de Noronha, Werica Bernardo, Alexandre Jesus Barros, Clovis Ryuichi Nakaie, Suma Imura Shimuta, Ismael Dale Cotrim Guerreiro da Silva, Samuel Marcos Ribeiro de Noronha

Departamento de Biofísica, Universidade Federal de S?o Paulo, S?o Paulo, Brazil.
Laboratorio de Cirurgia Translacional, Departamento de Cirurgia, Universidade Federal De Sao Paulo/Escola Paulista De Medicina, S?o Paulo, Brazil.
Laboratório de Ginecologia Molecular, Universidade Federal de S?o Paulo, S?o Paulo, Brazil.

DOI: 10.4236/jct.2013.47A010                

Abstract

Angiotensin-(1 - 7) [Ang-(1 - 7)] is an endogenous heptapeptide hormone of the renin-angiotensin system that has antiproliferative properties. The aim of this work was to evaluate the anti-proliferative and pro-apoptotic properties of Ang-(1 - 7) and of Ang-(1 - 7)-substituents 9-fluorenylmethyloxycarbonyl (Fmoc) e Ang II-derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) in normal (MCF10A) and in tumoral (MCF7) epithelial mammary cell lines. Both cell lines received an hCG and angiotensin peptides 24-hour treatment, in combination or alone followed by cell viability, apoptosis and cell cycle assays performed by flow cytometer (GUAVA). After hCG, Ang-(1 - 7), hCG + Ang-(1 - 7) and hCG + Ang-(1 - 7)-Fmoc treatments, MCF7 displayed cell viability decrease and mid-apoptosis increase. We also observed cell viability decrease in MCF10A after Ang-(1 - 7), Ang-(1 - 7) Fmoc and hCG + AngII Toac treatments. These cells had an increase in late apoptosis and necrosis after AngII Toac, hCG + Ang-(1 - 7) and hCG + Ang-(1 - 7)-Fmoc treatments. Regarding the cell cycle analysis, we did not observed any changes in cell cycle phases. In summary, cell viability was decreased and apoptosis (initial, mid and late) was increased after hCG and/or Ang-(1 - 7) peptides treatments. These results point out hCG and Ang-(1 - 7) as effective compounds to inhibit cell proliferation, since they decrease cell viability and increase apoptosis in both normal and in tumoral breast cells, being the effect more pronounced in the tumoral cell line. Our results support the idea of investigating more closely the putative use of these compounds as novel therapeutic agents for breast cancer.

Keywords

Angiotensin II; Angiotensin 1 - 7; Angiotensin II Type 1 Receptor (AT1R); Breast Cancer; Apoptosis; Human Chorionic Gonadotropin

Conflicts of Interest

The authors declare no conflicts of interest.

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