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Anti-Angiogenetic and Anti-Lymphangiogenic Effects of a Novel 2-Aminobenzimidazole Derivative, MFB
BACKGROUND AND PURPOSE: Benzimidazoles have attracted much attention over the last few decades due to their broad-spectrum pharmacological properties. Increasing evidence is showing the potential use of benzimidazoles as anti-angiogenic agents, although the mechanisms that impact angiogenesis remain...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251317/ https://www.ncbi.nlm.nih.gov/pubmed/35795066 http://dx.doi.org/10.3389/fonc.2022.862326 |
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author | Hsu, Ming-Jen Chen, Han-Kun Chen, Cheng-Yu Lien, Jin-Cherng Gao, Jing-Yan Huang, Yu-Han Hsu, Justin Bo-Kai Lee, Gilbert Aaron Huang, Shiu-Wen |
author_facet | Hsu, Ming-Jen Chen, Han-Kun Chen, Cheng-Yu Lien, Jin-Cherng Gao, Jing-Yan Huang, Yu-Han Hsu, Justin Bo-Kai Lee, Gilbert Aaron Huang, Shiu-Wen |
author_sort | Hsu, Ming-Jen |
collection | PubMed |
description | BACKGROUND AND PURPOSE: Benzimidazoles have attracted much attention over the last few decades due to their broad-spectrum pharmacological properties. Increasing evidence is showing the potential use of benzimidazoles as anti-angiogenic agents, although the mechanisms that impact angiogenesis remain to be fully defined. In this study, we aim to investigate the anti-angiogenic mechanisms of MFB, a novel 2-aminobenzimidazole derivative, to develop a novel angiogenesis inhibitor. EXPERIMENTAL APPROACH: MTT, BrdU, migration and invasion assays, and immunoblotting were employed to examine MFB’s effects on vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration, invasion, as well as signaling molecules activation. The anti-angiogenic effects of MFB were analyzed by tube formation, aorta ring sprouting, and matrigel plug assays. We also used a mouse model of lung metastasis to determine the MFB’s anti-metastatic effects. KEY RESULTS: MFB suppressed cell proliferation, migration, invasion, and endothelial tube formation of VEGF-A-stimulated human umbilical vascular endothelial cells (HUVECs) or VEGF-C-stimulated lymphatic endothelial cells (LECs). MFB suppressed VEGF-A and VEGF-C signaling in HUVECs or LECs. In addition, MFB reduced VEGF-A- or tumor cells-induced neovascularization in vivo. MFB also diminished B16F10 melanoma lung metastasis. The molecular docking results further showed that MFB may bind to VEGFR-2 rather than VEGF-A with high affinity. CONCLUSIONS AND IMPLICATIONS: These observations indicated that MFB may target VEGF/VEGFR signaling to suppress angiogenesis and lymphangiogenesis. It also supports the role of MFB as a potential lead in developing novel agents for the treatment of angiogenesis- or lymphangiogenesis-associated diseases and cancer. |
format | Online Article Text |
id | pubmed-9251317 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92513172022-07-05 Anti-Angiogenetic and Anti-Lymphangiogenic Effects of a Novel 2-Aminobenzimidazole Derivative, MFB Hsu, Ming-Jen Chen, Han-Kun Chen, Cheng-Yu Lien, Jin-Cherng Gao, Jing-Yan Huang, Yu-Han Hsu, Justin Bo-Kai Lee, Gilbert Aaron Huang, Shiu-Wen Front Oncol Oncology BACKGROUND AND PURPOSE: Benzimidazoles have attracted much attention over the last few decades due to their broad-spectrum pharmacological properties. Increasing evidence is showing the potential use of benzimidazoles as anti-angiogenic agents, although the mechanisms that impact angiogenesis remain to be fully defined. In this study, we aim to investigate the anti-angiogenic mechanisms of MFB, a novel 2-aminobenzimidazole derivative, to develop a novel angiogenesis inhibitor. EXPERIMENTAL APPROACH: MTT, BrdU, migration and invasion assays, and immunoblotting were employed to examine MFB’s effects on vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration, invasion, as well as signaling molecules activation. The anti-angiogenic effects of MFB were analyzed by tube formation, aorta ring sprouting, and matrigel plug assays. We also used a mouse model of lung metastasis to determine the MFB’s anti-metastatic effects. KEY RESULTS: MFB suppressed cell proliferation, migration, invasion, and endothelial tube formation of VEGF-A-stimulated human umbilical vascular endothelial cells (HUVECs) or VEGF-C-stimulated lymphatic endothelial cells (LECs). MFB suppressed VEGF-A and VEGF-C signaling in HUVECs or LECs. In addition, MFB reduced VEGF-A- or tumor cells-induced neovascularization in vivo. MFB also diminished B16F10 melanoma lung metastasis. The molecular docking results further showed that MFB may bind to VEGFR-2 rather than VEGF-A with high affinity. CONCLUSIONS AND IMPLICATIONS: These observations indicated that MFB may target VEGF/VEGFR signaling to suppress angiogenesis and lymphangiogenesis. It also supports the role of MFB as a potential lead in developing novel agents for the treatment of angiogenesis- or lymphangiogenesis-associated diseases and cancer. Frontiers Media S.A. 2022-06-20 /pmc/articles/PMC9251317/ /pubmed/35795066 http://dx.doi.org/10.3389/fonc.2022.862326 Text en Copyright © 2022 Hsu, Chen, Chen, Lien, Gao, Huang, Hsu, Lee and Huang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Hsu, Ming-Jen Chen, Han-Kun Chen, Cheng-Yu Lien, Jin-Cherng Gao, Jing-Yan Huang, Yu-Han Hsu, Justin Bo-Kai Lee, Gilbert Aaron Huang, Shiu-Wen Anti-Angiogenetic and Anti-Lymphangiogenic Effects of a Novel 2-Aminobenzimidazole Derivative, MFB |
title | Anti-Angiogenetic and Anti-Lymphangiogenic Effects of a Novel 2-Aminobenzimidazole Derivative, MFB |
title_full | Anti-Angiogenetic and Anti-Lymphangiogenic Effects of a Novel 2-Aminobenzimidazole Derivative, MFB |
title_fullStr | Anti-Angiogenetic and Anti-Lymphangiogenic Effects of a Novel 2-Aminobenzimidazole Derivative, MFB |
title_full_unstemmed | Anti-Angiogenetic and Anti-Lymphangiogenic Effects of a Novel 2-Aminobenzimidazole Derivative, MFB |
title_short | Anti-Angiogenetic and Anti-Lymphangiogenic Effects of a Novel 2-Aminobenzimidazole Derivative, MFB |
title_sort | anti-angiogenetic and anti-lymphangiogenic effects of a novel 2-aminobenzimidazole derivative, mfb |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251317/ https://www.ncbi.nlm.nih.gov/pubmed/35795066 http://dx.doi.org/10.3389/fonc.2022.862326 |
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