Cargando…

Anti-Angiogenic and Anti-Metastatic Activity of Synthetic Phosphoethanolamine

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. I...

Descripción completa

Detalles Bibliográficos
Autores principales: Ferreira, Adilson Kleber, Freitas, Vanessa Morais, Levy, Débora, Ruiz, Jorge Luiz Mária, Bydlowski, Sergio Paulo, Rici, Rose Eli Grassi, Filho, Otaviano Mendonça R., Chierice, Gilberto Orivaldo, Maria, Durvanei Augusto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597720/
https://www.ncbi.nlm.nih.gov/pubmed/23516420
http://dx.doi.org/10.1371/journal.pone.0057937
_version_ 1782262683838447616
author Ferreira, Adilson Kleber
Freitas, Vanessa Morais
Levy, Débora
Ruiz, Jorge Luiz Mária
Bydlowski, Sergio Paulo
Rici, Rose Eli Grassi
Filho, Otaviano Mendonça R.
Chierice, Gilberto Orivaldo
Maria, Durvanei Augusto
author_facet Ferreira, Adilson Kleber
Freitas, Vanessa Morais
Levy, Débora
Ruiz, Jorge Luiz Mária
Bydlowski, Sergio Paulo
Rici, Rose Eli Grassi
Filho, Otaviano Mendonça R.
Chierice, Gilberto Orivaldo
Maria, Durvanei Augusto
author_sort Ferreira, Adilson Kleber
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3597720
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-35977202013-03-20 Anti-Angiogenic and Anti-Metastatic Activity of Synthetic Phosphoethanolamine Ferreira, Adilson Kleber Freitas, Vanessa Morais Levy, Débora Ruiz, Jorge Luiz Mária Bydlowski, Sergio Paulo Rici, Rose Eli Grassi Filho, Otaviano Mendonça R. Chierice, Gilberto Orivaldo Maria, Durvanei Augusto PLoS One Research Article 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. Public Library of Science 2013-03-14 /pmc/articles/PMC3597720/ /pubmed/23516420 http://dx.doi.org/10.1371/journal.pone.0057937 Text en © 2013 Ferreira et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ferreira, Adilson Kleber
Freitas, Vanessa Morais
Levy, Débora
Ruiz, Jorge Luiz Mária
Bydlowski, Sergio Paulo
Rici, Rose Eli Grassi
Filho, Otaviano Mendonça R.
Chierice, Gilberto Orivaldo
Maria, Durvanei Augusto
Anti-Angiogenic and Anti-Metastatic Activity of Synthetic Phosphoethanolamine
title Anti-Angiogenic and Anti-Metastatic Activity of Synthetic Phosphoethanolamine
title_full Anti-Angiogenic and Anti-Metastatic Activity of Synthetic Phosphoethanolamine
title_fullStr Anti-Angiogenic and Anti-Metastatic Activity of Synthetic Phosphoethanolamine
title_full_unstemmed Anti-Angiogenic and Anti-Metastatic Activity of Synthetic Phosphoethanolamine
title_short Anti-Angiogenic and Anti-Metastatic Activity of Synthetic Phosphoethanolamine
title_sort anti-angiogenic and anti-metastatic activity of synthetic phosphoethanolamine
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597720/
https://www.ncbi.nlm.nih.gov/pubmed/23516420
http://dx.doi.org/10.1371/journal.pone.0057937
work_keys_str_mv AT ferreiraadilsonkleber antiangiogenicandantimetastaticactivityofsyntheticphosphoethanolamine
AT freitasvanessamorais antiangiogenicandantimetastaticactivityofsyntheticphosphoethanolamine
AT levydebora antiangiogenicandantimetastaticactivityofsyntheticphosphoethanolamine
AT ruizjorgeluizmaria antiangiogenicandantimetastaticactivityofsyntheticphosphoethanolamine
AT bydlowskisergiopaulo antiangiogenicandantimetastaticactivityofsyntheticphosphoethanolamine
AT riciroseeligrassi antiangiogenicandantimetastaticactivityofsyntheticphosphoethanolamine
AT filhootavianomendoncar antiangiogenicandantimetastaticactivityofsyntheticphosphoethanolamine
AT chiericegilbertoorivaldo antiangiogenicandantimetastaticactivityofsyntheticphosphoethanolamine
AT mariadurvaneiaugusto antiangiogenicandantimetastaticactivityofsyntheticphosphoethanolamine