human Chorionic Gonadotropin and Deriveted-Angiotensin Peptides Effects on Cell Viability and on Apoptosis in Tumoral (MCF-7) and in Normal (MCF10A) Epithelial Breast Cells

摘要

Angiotensin-(1-7) [Ang-(1-7)] is an endogenous heptapeptide hormone of the renin-angiotensin systemthat has antiproliferative properties. The aim of this work was to evaluate the anti-proliferative and pro-apoptoticproperties of Ang-(1-7) and of Ang-(1-7)- substituents 9-fluorenylmethyloxycarbonyl (Fmoc) e Ang IIderivativescontaining 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 andangiotensin peptides 24-hour treatment, in combination or alone followed by cell viability, apoptosis and cellcycle 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 observedcell viability decrease in MCF10A after Ang-(1-7), Ang-(1-7) Fmoc and hCG+AngII Toac treatments. Thesecells 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. Insummary, 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 cellproliferation, 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 moreclosely the putative use of these compounds as novel therapeutic agents for breast cancer.