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Fenghua Kang1, Jiayi Zhu1, Jianbing Wu1
1State Key Laboratory of Natural Medicines , Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases , Center of Drug Discovery , China Pharmaceutical University , Nanjing 210009 , China . Email: zyhtgd@163.com ;
Chemical Science
|September 14, 2018
Summary
A new compound selectively targets and inhibits microvesicle formation in triple-negative breast cancer (TNBC) cells. This novel approach reduces TNBC metastasis and offers a potential new therapy for this aggressive cancer.
Area of Science:
- Oncology
- Molecular Biology
- Medicinal Chemistry
Background:
- Triple-negative breast cancer (TNBC) is highly metastatic with limited treatment options.
- Microvesicle (MV) formation is a key mechanism driving TNBC metastasis.
Purpose of the Study:
- To develop a novel therapeutic strategy targeting MV generation for TNBC intervention.
- To synthesize and evaluate novel compounds as potential inhibitors of TNBC metastasis.
Main Methods:
- Design and synthesis of O2-3-Aminopropyl diazeniumdiolates (3a-f) activated by lysyloxidase.
- In vitro assessment of compound 3f's effects on TNBC cell proliferation, adhesion, invasion, and migration.
- In vivo evaluation of compound 3f's efficacy in suppressing TNBC growth and metastasis, including analysis of MV formation and epigenetic modifications.
Main Results:
- Compound 3f selectively releases nitric oxide (NO) in TNBC cells.
- 3f inhibits TNBC cell proliferation and reduces adhesion, invasion, and migration in vitro.
- In vivo, 3f significantly suppresses tumor growth and metastasis by attenuating MV formation via epigenetic modulation of miR-203/RAB22A in an NO-dependent manner.
Conclusions:
- Novel NO-releasing compounds can effectively inhibit TNBC metastasis.
- Compound 3f demonstrates potential as a therapeutic agent for highly metastatic TNBC.
- This study provides the first evidence of NO donors acting as epigenetic modulators against metastatic TNBC.