TITLE:
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
AUTHORS:
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
KEYWORDS:
Angiotensin II; Angiotensin 1 - 7; Angiotensin II Type 1 Receptor (AT1R); Breast Cancer; Apoptosis; Human Chorionic Gonadotropin
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.7A,
July
23,
2013
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.