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O (2)-3-Aminopropyl diazeniumdiolates suppress the progression of highly metastatic triple-negative breast cancer by inhibition of microvesicle formation via nitric oxide-based epigenetic regulation
Currently, there is no effective therapy for the treatment of highly metastatic triple-negative breast cancer (TNBC). Microvesicle (MV) formation is crucial for the metastasis of TNBC. Here we report a novel strategy to inhibit the generation of MVs for the intervention of TNBC. O(2)-3-Aminopropyl d...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124901/ https://www.ncbi.nlm.nih.gov/pubmed/30210764 http://dx.doi.org/10.1039/c8sc00167g |
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author | Kang, Fenghua Zhu, Jiayi Wu, Jianbing Lv, Tian Xiang, Hua Tian, Jide Zhang, Yihua Huang, Zhangjian |
author_facet | Kang, Fenghua Zhu, Jiayi Wu, Jianbing Lv, Tian Xiang, Hua Tian, Jide Zhang, Yihua Huang, Zhangjian |
author_sort | Kang, Fenghua |
collection | PubMed |
description | Currently, there is no effective therapy for the treatment of highly metastatic triple-negative breast cancer (TNBC). Microvesicle (MV) formation is crucial for the metastasis of TNBC. Here we report a novel strategy to inhibit the generation of MVs for the intervention of TNBC. O(2)-3-Aminopropyl diazeniumdiolates 3a–f are designed and synthesized, which can be activated by lysyloxidase over-expressed in TNBC cells. The most active compound 3f is able to selectively release high levels of NO in TNBC cells, inhibit the cell proliferation, and reduce the adhesion, invasion and migration of TNBC cells in vitro. Furthermore, 3f significantly suppresses the growth and metastasis of implanted TNBC in vivo through attenuating MV formation by an epigenetic modification of miR-203/RAB22A expression in an NO-dependent manner, providing the first evidence of NO donor(s) acting as epigenetic modulators to fight highly metastatic TNBC. |
format | Online Article Text |
id | pubmed-6124901 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-61249012018-09-12 O (2)-3-Aminopropyl diazeniumdiolates suppress the progression of highly metastatic triple-negative breast cancer by inhibition of microvesicle formation via nitric oxide-based epigenetic regulation Kang, Fenghua Zhu, Jiayi Wu, Jianbing Lv, Tian Xiang, Hua Tian, Jide Zhang, Yihua Huang, Zhangjian Chem Sci Chemistry Currently, there is no effective therapy for the treatment of highly metastatic triple-negative breast cancer (TNBC). Microvesicle (MV) formation is crucial for the metastasis of TNBC. Here we report a novel strategy to inhibit the generation of MVs for the intervention of TNBC. O(2)-3-Aminopropyl diazeniumdiolates 3a–f are designed and synthesized, which can be activated by lysyloxidase over-expressed in TNBC cells. The most active compound 3f is able to selectively release high levels of NO in TNBC cells, inhibit the cell proliferation, and reduce the adhesion, invasion and migration of TNBC cells in vitro. Furthermore, 3f significantly suppresses the growth and metastasis of implanted TNBC in vivo through attenuating MV formation by an epigenetic modification of miR-203/RAB22A expression in an NO-dependent manner, providing the first evidence of NO donor(s) acting as epigenetic modulators to fight highly metastatic TNBC. Royal Society of Chemistry 2018-08-03 /pmc/articles/PMC6124901/ /pubmed/30210764 http://dx.doi.org/10.1039/c8sc00167g Text en This journal is © The Royal Society of Chemistry 2018 http://creativecommons.org/licenses/by-nc/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported Licence (CC BY-NC 3.0) |
spellingShingle | Chemistry Kang, Fenghua Zhu, Jiayi Wu, Jianbing Lv, Tian Xiang, Hua Tian, Jide Zhang, Yihua Huang, Zhangjian O (2)-3-Aminopropyl diazeniumdiolates suppress the progression of highly metastatic triple-negative breast cancer by inhibition of microvesicle formation via nitric oxide-based epigenetic regulation |
title |
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(2)-3-Aminopropyl diazeniumdiolates suppress the progression of highly metastatic triple-negative breast cancer by inhibition of microvesicle formation via nitric oxide-based epigenetic regulation
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title_full |
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(2)-3-Aminopropyl diazeniumdiolates suppress the progression of highly metastatic triple-negative breast cancer by inhibition of microvesicle formation via nitric oxide-based epigenetic regulation
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title_fullStr |
O
(2)-3-Aminopropyl diazeniumdiolates suppress the progression of highly metastatic triple-negative breast cancer by inhibition of microvesicle formation via nitric oxide-based epigenetic regulation
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title_full_unstemmed |
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(2)-3-Aminopropyl diazeniumdiolates suppress the progression of highly metastatic triple-negative breast cancer by inhibition of microvesicle formation via nitric oxide-based epigenetic regulation
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title_short |
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(2)-3-Aminopropyl diazeniumdiolates suppress the progression of highly metastatic triple-negative breast cancer by inhibition of microvesicle formation via nitric oxide-based epigenetic regulation
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title_sort | o
(2)-3-aminopropyl diazeniumdiolates suppress the progression of highly metastatic triple-negative breast cancer by inhibition of microvesicle formation via nitric oxide-based epigenetic regulation |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124901/ https://www.ncbi.nlm.nih.gov/pubmed/30210764 http://dx.doi.org/10.1039/c8sc00167g |
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