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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Anti-Angiogenic and Anti-Metastatic Activity of Synthetic Phosphoethanolamine

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Autor(es):
Ferreira, Adilson Kleber [1, 2] ; Freitas, Vanessa Morais [3] ; Levy, Debora [4] ; Maria Ruiz, Jorge Luiz [4] ; Bydlowski, Sergio Paulo [4] ; Grassi Rici, Rose Eli [5] ; Filho, Otaviano Mendonca R. [6] ; Chierice, Gilberto Orivaldo [7] ; Maria, Durvanei Augusto [1, 2]
Número total de Autores: 9
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 Cell & Dev Biol, Sao Paulo - Brazil
[4] Univ Sao Paulo, Fac Med, Lab Genet & Mol Hematol LIM 31, Sao Paulo - Brazil
[5] Univ Sao Paulo, Dept Surg, Fac Vet Med & Zootecny, Sao Paulo - Brazil
[6] Univ Uberaba, Uberaba, MG - Brazil
[7] Univ Sao Paulo, Dept Chem & Polymers Technol, Sao Carlos, SP - Brazil
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 8, n. 3 MAR 14 2013.
Citações Web of Science: 23
Resumo

Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer, and represents the third most common urological malignancy. Despite the advent of targeted therapies for RCC and the improvement of the lifespan of patients, its cost-effectiveness restricted the therapeutic efficacy. In a recent report, we showed that synthetic phosphoethanolamine (Pho-s) has a broad antitumor activity on a variety of tumor cells and showed potent inhibitor effects on tumor progress in vivo. Methodology/Principal Findings: We show that murine renal carcinoma (Renca) is more sensitive to Pho-s when compared to normal immortalized rat proximal tubule cells (IRPTC) and human umbilical vein endothelial cells (HUVEC). In vitro anti-angiogenic activity assays show that Pho-s inhibits endothelial cell proliferation, migration and tube formation. In addition, Pho-s has anti-proliferative effects on HUVEC by inducing a cell cycle arrest at the G2/M phase. It causes a decrease in cyclin D1 mRNA, VEGFR1 gene transcription and VEGFR1 receptor expression. Pho-s also induces nuclear fragmentation and affects the organization of the cytoskeleton through the disruption of actin filaments. Additionally, Pho-s induces apoptosis through the mitochondrial pathway. The putative therapeutic potential of Pho-s was validated in a renal carcinoma model, on which our remarkable in vivo results show that Pho-s potentially inhibits lung metastasis in nude mice, with a superior efficacy when compared to Sunitinib. Conclusions/Significance: Taken together, our findings provide evidence that Pho-s is a compound that potently inhibits lung metastasis, suggesting that it is a promising novel candidate drug for future developments. (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 - Avaliação das propriedades anti-tumorais da fosfoetanolamina sintética 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 - Avaliação das propriedades antitumorais e apoptóticas da fosfoetanolamina sintética em modelos experimentais
Beneficiário:Adilson Kleber Ferreira
Linha de fomento: Bolsas no Brasil - Mestrado