Anti-angiogenic and anti-metastatic activity of synthetic phosphoethanolamine.
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 r...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3597720?pdf=render |
| _version_ | 1818360313343377408 |
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| author | Adilson Kleber Ferreira Vanessa Morais Freitas Débora Levy Jorge Luiz Mária Ruiz Sergio Paulo Bydlowski Rose Eli Grassi Rici Otaviano Mendonça R Filho Gilberto Orivaldo Chierice Durvanei Augusto Maria |
| author_facet | Adilson Kleber Ferreira Vanessa Morais Freitas Débora Levy Jorge Luiz Mária Ruiz Sergio Paulo Bydlowski Rose Eli Grassi Rici Otaviano Mendonça R Filho Gilberto Orivaldo Chierice Durvanei Augusto Maria |
| author_sort | Adilson Kleber Ferreira |
| collection | DOAJ |
| description | 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.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.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. |
| first_indexed | 2024-12-13T20:58:48Z |
| format | Article |
| id | doaj.art-efe250c9eddc42738ca8fbd9ca39748d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T20:58:48Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-efe250c9eddc42738ca8fbd9ca39748d2022-12-21T23:31:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5793710.1371/journal.pone.0057937Anti-angiogenic and anti-metastatic activity of synthetic phosphoethanolamine.Adilson Kleber FerreiraVanessa Morais FreitasDébora LevyJorge Luiz Mária RuizSergio Paulo BydlowskiRose Eli Grassi RiciOtaviano Mendonça R FilhoGilberto Orivaldo ChiericeDurvanei Augusto MariaRenal 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.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.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.http://europepmc.org/articles/PMC3597720?pdf=render |
| spellingShingle | Adilson Kleber Ferreira Vanessa Morais Freitas Débora Levy Jorge Luiz Mária Ruiz Sergio Paulo Bydlowski Rose Eli Grassi Rici Otaviano Mendonça R Filho Gilberto Orivaldo Chierice Durvanei Augusto Maria Anti-angiogenic and anti-metastatic activity of synthetic phosphoethanolamine. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3597720?pdf=render |
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