Synthetic phosphoethanolamine a precursor of membrane phospholipids reduce tumor growth in mice bearing melanoma B16-F10 and in vitro induce apoptosis and arrest in G2/M phase

Autor(es)

Ferreira, Adilson Kleber ^[1] ; Meneguelo, Renato ^[2] ; Navarro Marques, Fabio Luiz ^[3] ; Radin, Adriano ^[3] ; Filho, Otaviano Mendonca R. ^[4] ; Claro Neto, Salvador ^[2] ; Chierice, Gilberto Orivaldo ^[2] ; Maria, Durvanei Augusto ^[1]

Afiliação do(s) autor(es)

^[1] Butantan Inst, Biochem & Biophys Lab, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Chem & Polymers Technol, Sao Carlos, SP - Brazil

^[3] Univ Sao Paulo, Fac Med, Dept Radiol, Lab Clin Radioisotopia, Sao Paulo - Brazil

^[4] Univ Uberaba, UNIUBE, Uberaba, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOMEDICINE & PHARMACOTHERAPY; v. 66, n. 7, p. 541-548, OCT 2012.
• Citações Web of Science: 14

Resumo

Phosphoethanolamine (Pho-s) is a compound involved in phospholipid turnover, acting as a substrate for many phospholipids of the cell membranes, especially phosphatidylcholine. We recently reported that synthetic Pho-s has potent effects on a wide variety of tumor cells. To determine if Pho-s has a potential antitumor activity, in this study we evaluated the activity of Pho-s against the B16-F10 melanoma both in vitro and in mice bearing a dorsal tumor. The treatment of B16F10 cells with Pho-s resulted in a dose-dependent inhibition of cell proliferation. At low concentrations, this activity appears to be involved in the arrest of the cell cycle at G2/M, while at high concentrations Pho-s induces apoptosis. In accordance with these results, the loss of mitochondrial potential and increased caspase-3 activity suggest that Phos has dual antitumor effects; i.e. it induces apoptosis at high concentrations and modulates the cell cycle at lower concentrations. In vivo, we evaluated the effect of Pho-s in mice bearing B16-F10 melanoma. The results show that Pho-s reduces the tumoral volume increasing survival rate. Furthermore, the tumor doubling time and tumor delays were substantially reduced when compared with untreated mice. Histological analyses reveal that Pho-s induces changes in cell morphology, typical characteristics of apoptosis, in addition the large areas of necrosis correlating with a reduction of tumor size. The results presented here support the hypothesis that Pho-s has antitumor effects by the induction of apoptosis as well as the inhibition of cell proliferation by arrest at G2/M. Thus, Pho-s can be regarded as a promising agent for the treatment of melanoma. Published by Elsevier Masson SAS. (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: 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
• 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