Anti-Angiogenic and Anti-Metastatic Activity of Synthetic Phosphoethanolamine

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art_FERREIRA_Anti_Angiogenic_and_Anti_Metastatic_Activity_of_Synthetic_2013.PDF (13.42 MB)
Citações na Scopus
36
Tipo de produção
article
Data de publicação
2013
Editora
PUBLIC LIBRARY SCIENCE
DOI
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Scopus
Web of Science
PubMed
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Título do Volume
Autores
FREITAS, Vanessa Morais
RUIZ, Jorge Luiz Maria
RICI, Rose Eli Grassi
FILHO, Otaviano Mendonca R.
CHIERICE, Gilberto Orivaldo
MARIA, Durvanei Augusto
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
PLOS ONE, v.8, n.3, article ID e57937, 14p, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
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.
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URI
https://observatorio.fm.usp.br/handle/OPI/1749
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/31
Artigos e Materiais de Revistas Científicas - ODS/03