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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

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Abstract

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. O2-3-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.

Graphical abstract: O2-3-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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Publication details

The article was received on 11 Jan 2018, accepted on 06 Jul 2018 and first published on 03 Aug 2018


Article type: Edge Article
DOI: 10.1039/C8SC00167G
Citation: Chem. Sci., 2018, Advance Article
  • Open access: Creative Commons BY-NC license
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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

    F. Kang, J. Zhu, J. Wu, T. Lv, H. Xiang, J. Tian, Y. Zhang and Z. Huang, Chem. Sci., 2018, Advance Article , DOI: 10.1039/C8SC00167G

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