Anti-Angiogenic and Anti-Metastatic Activity of Synthetic Phosphoethanolamine

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]}

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

• 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
• Modalidade de apoio: 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
• Modalidade de apoio: 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
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica