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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...

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Autores principales: Kang, Fenghua, Zhu, Jiayi, Wu, Jianbing, Lv, Tian, Xiang, Hua, Tian, Jide, Zhang, Yihua, Huang, Zhangjian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2018
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.
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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 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_full 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_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
title_full_unstemmed 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_short 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_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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