2. Academic Validation
  3. The BR2 peptide associated with 2-aminoethyl dihydrogen phosphate is a formulation with antiproliferative potential for a triple-negative breast cancer model

The BR2 peptide associated with 2-aminoethyl dihydrogen phosphate is a formulation with antiproliferative potential for a triple-negative breast cancer model

  • Biomed Pharmacother. 2022 Sep:153:113398. doi: 10.1016/j.biopha.2022.113398.
Laertty Garcia de Sousa Cabral 1,  Henrique Hesse 2,  Katielle Albuquerque Freire 3,  Cyntia Silva de Oliveira 3,  Cibele Nicolaski Pedron 4,  Monique Gonçalves Alves 2,  Julio Pacheco Carlstron 2,  Jean-Luc Poyet 5,  Vani X Oliveira Jr 6,  Durvanei A Maria 7
Affiliations

Affiliations

  • 1 Faculty of Medicine, University of Sao Paulo, FMUSP, Sao Paulo, Brazil; Laboratory of Development and Innovation, Butantan Institute, Sao Paulo, Brazil. Electronic address: laertty.c@usp.br.
  • 2 Faculty of Medicine, University of Sao Paulo, FMUSP, Sao Paulo, Brazil; Laboratory of Development and Innovation, Butantan Institute, Sao Paulo, Brazil.
  • 3 Federal University of Sao Paulo, UNIFESP, Sao Paulo, Brazil.
  • 4 Federal University of ABC, Center for Natural and Human Sciences, Santo Andre, Brazil.
  • 5 Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France; INSERM UMRS976, Institut De Recherche Saint-Louis, Hôpital Saint-Louis, Paris, France.
  • 6 Federal University of Sao Paulo, UNIFESP, Sao Paulo, Brazil; Federal University of ABC, Center for Natural and Human Sciences, Santo Andre, Brazil.
  • 7 Faculty of Medicine, University of Sao Paulo, FMUSP, Sao Paulo, Brazil; Laboratory of Development and Innovation, Butantan Institute, Sao Paulo, Brazil. Electronic address: durvanei.maria@butantan.gov.br.
PMID: 36076530 DOI: 10.1016/j.biopha.2022.113398
Abstract

Triple-negative breast Cancer is the most aggressive subtype of breast Cancer, with worse clinical evolution and tumor-free survival, leading to the need to develop new effective therapies for its control. The present study evaluated the action of tumor-penetrating peptide BR2 associated with 2-aminoethyl dihydrogen phosphate (2-AEH2P) on triple-negative breast tumor cells. Cell viability was evaluated by the MTT colorimetric method, mitochondrial electrical potential, and proteins involved in cell proliferation and death control were evaluated by flow cytometry and structural and morphological analysis by confocal microscopy. The results obtained showed that the peptide BR2 and the association 2-AEH2P + BR2 promoted significant cytotoxicity in tumor lines, compared to 2-AEH2P alone. In addition, the association 2-AEH2P + BR2 promoted tumor cells arrest in the G0/G1 phases. Interestingly, both treatments modulated the expression of markers CD44, CD34, CD24, cyclin D1, and Bcl-2, increased p21, Bax, and released cytochrome c. The association proved to be more effective, providing modulation of proteins involved in cell death and senescence, more pronounced cytotoxicity for tumor cells compared to normal cells, and the reduction of markers related to aggressiveness profile, progression, and tumor metastasis.

Keywords

Monophosphoester; Nano molecules; Peptide; Synergism; Triple-negative breast cancer.

Figures
Products