Synthetic phosphoethanolamine induces cell cycle arrest and apoptosis in human breast cancer MCF-7 cells through the mitochondrial pathway

Autor(es)

Ferreira, Adilson Kleber ^{[1, 2]} ; Meneguelo, Renato ^[3] ; Pereira, Alexandre ^[4] ; Filho, Otaviano Mendonca R. ^[5] ; Chierice, Gilberto Orivaldo ^[3] ; Maria, Durvanei Augusto ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Sao Paulo - Brazil

^[2] Butantan Inst, Biochem & Biophys Lab, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Chem & Polymers Technol, Sao Carlos, SP - Brazil

^[4] Butantan Inst, Genet Lab, Sao Paulo - Brazil

^[5] Univ Uberaba, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOMEDICINE & PHARMACOTHERAPY; v. 67, n. 6, p. 481-487, JUL 2013.
• Citações Web of Science: 23

Resumo

Phosphoethanolamine (Pho-s) is a compound involved in phospholipid turnover, acting as a substrate for many phospholipids of the cell membranes. In a recent study, we showed that Pho-s has antitumor effect in the several tumor cells. In this study we evaluated the antitumor activity of synthetic Pho-s on MCF-7 breast cancer cells. Here we demonstrate that Pho-s is cytotoxic to MCF-7 cells in a dose-dependent manner, while it is cytotoxic to MCF10 only at higher concentrations. In addition, Pho-s induces a disruption in mitochondrial membrane potential (Delta psi m). Furthermore, Pho-s induces mitochondria aggregates in the cytoplasm and DNA fragmentation of MCF-7 cells visualized by confocal microscopy. In agreement with the reduction on Delta psi m, we showed that Pho-s induces apoptosis followed by an increase in cytochrome c expression and capase-3-like activity in MCF-7 cells. Our results demonstrate that Pho-s induces a cell cycle arrest in the G1 phase through an inhibition of cyclin D1 and stimulates p53. An additional highlight of this study is the finding that Pho-s inhibits Bcl-2, inducing apoptosis through the mitochondrial pathway. Taken together, these results show that Pho-s is a promising compound in the fight against cancer. (C) 2013 Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 10/50220-9 - Alquil fosfatado sintético precursor dos fosfolipídios de membrana celular com potencial efeito antitumoral e apoptótico em modelos de tumores experimentais
• Beneficiário: Adilson Kleber Ferreira
• Linha de fomento: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 08/56089-1 - Avaliacao das propriedades antitumorais e apoptoticas da fosfoetanolamina sintetica em modelos experimentais
• Beneficiário: Adilson Kleber Ferreira
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 07/50571-3 - Avaliacao das propriedades anti-tumorais da fosfoetanolamina sintetica in vitro e in vivo no melanoma b16f10.
• Beneficiário: Adilson Kleber Ferreira
• Linha de fomento: Bolsas no Brasil - Iniciação Científica