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Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis
Angiogenesis is a vital step during the process of oncogenesis of a lot of tumors, with no exception in bladder cancer. One of the useful strategies for the development of new drugs against cancer is targeting angiogenesis. In the present study, we found that a small-molecule natural product, which...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499454/ https://www.ncbi.nlm.nih.gov/pubmed/30910851 http://dx.doi.org/10.1042/BSR20190155 |
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author | Hai-rong, Cai Xiang, Huang Xiao-rong, Zhang |
author_facet | Hai-rong, Cai Xiang, Huang Xiao-rong, Zhang |
author_sort | Hai-rong, Cai |
collection | PubMed |
description | Angiogenesis is a vital step during the process of oncogenesis of a lot of tumors, with no exception in bladder cancer. One of the useful strategies for the development of new drugs against cancer is targeting angiogenesis. In the present study, we found that a small-molecule natural product, which belonged to the β-carboline alkaloid, named harmine, could strongly inhibit tumor angiogenesis thus exhibiting its ideal treatment efficacy in bladder cancer. In vivo study verified that harmine had the effect of inhibition on human bladder tumor xenograft growth. The inhibitory effect of harmine to bladder cancer growth was coordinated by the effects shown on angiogenesis. To further explore the pharmacological activities of harmine, we tested harmine’s influence on blood vessel formation and found that harmine effectively blocked the microvessel sprouting in rat aortic ring assay when stimulated by vascular endothelial growth factor (VEGF). Furthermore, harmine inhibited human umbilical vein endothelial cell (HUVEC) proliferation as well as chemotactic motility, and when we treated HUVEC cell with harmine, the formation of capillary-like structures was also restrained. Moreover, harmine induced bladder cancer cell apoptosis through triggering the caspase-dependent apoptotic pathway and the downstream vascular endothelial growth factor receptor 2 (VEGFR2) kinase pathway was down-regulated, thus suppressing tumor development signals. Herein, our study demonstrated that natural product harmine might have potential in curing human bladder tumor because of its pharmacological function on tumor angiogenesis, trigged by VEGFR2 signaling pathways. |
format | Online Article Text |
id | pubmed-6499454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64994542019-05-16 Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis Hai-rong, Cai Xiang, Huang Xiao-rong, Zhang Biosci Rep Research Articles Angiogenesis is a vital step during the process of oncogenesis of a lot of tumors, with no exception in bladder cancer. One of the useful strategies for the development of new drugs against cancer is targeting angiogenesis. In the present study, we found that a small-molecule natural product, which belonged to the β-carboline alkaloid, named harmine, could strongly inhibit tumor angiogenesis thus exhibiting its ideal treatment efficacy in bladder cancer. In vivo study verified that harmine had the effect of inhibition on human bladder tumor xenograft growth. The inhibitory effect of harmine to bladder cancer growth was coordinated by the effects shown on angiogenesis. To further explore the pharmacological activities of harmine, we tested harmine’s influence on blood vessel formation and found that harmine effectively blocked the microvessel sprouting in rat aortic ring assay when stimulated by vascular endothelial growth factor (VEGF). Furthermore, harmine inhibited human umbilical vein endothelial cell (HUVEC) proliferation as well as chemotactic motility, and when we treated HUVEC cell with harmine, the formation of capillary-like structures was also restrained. Moreover, harmine induced bladder cancer cell apoptosis through triggering the caspase-dependent apoptotic pathway and the downstream vascular endothelial growth factor receptor 2 (VEGFR2) kinase pathway was down-regulated, thus suppressing tumor development signals. Herein, our study demonstrated that natural product harmine might have potential in curing human bladder tumor because of its pharmacological function on tumor angiogenesis, trigged by VEGFR2 signaling pathways. Portland Press Ltd. 2019-05-02 /pmc/articles/PMC6499454/ /pubmed/30910851 http://dx.doi.org/10.1042/BSR20190155 Text en © 2019 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Articles Hai-rong, Cai Xiang, Huang Xiao-rong, Zhang Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis |
title | Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis |
title_full | Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis |
title_fullStr | Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis |
title_full_unstemmed | Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis |
title_short | Harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis |
title_sort | harmine suppresses bladder tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499454/ https://www.ncbi.nlm.nih.gov/pubmed/30910851 http://dx.doi.org/10.1042/BSR20190155 |
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