1. Structure-Based Design of a Selective Class I Histone Deacetylase (HDAC) Near-Infrared (NIR) Probe for Epigenetic Regulation Detection in Triple-Negative Breast Cancer (TNBC)
- Author
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Dale J. Hamilton, Zhiyi Liu, Sheng Jiang, Dong Chen, Yatao Qiu, Kuojun Zhang, Yiwu Yao, Feng Li, and Zheng Li
- Subjects
Poor prognosis ,Lung Neoplasms ,Mice, Nude ,Triple Negative Breast Neoplasms ,Cyclic depsipeptide ,01 natural sciences ,Histone Deacetylases ,Epigenesis, Genetic ,Malignant transformation ,03 medical and health sciences ,Breast cancer ,Cell Line, Tumor ,Depsipeptides ,Drug Discovery ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Fluorometry ,Epigenetics ,Triple-negative breast cancer ,030304 developmental biology ,Vorinostat ,0303 health sciences ,Chemistry ,Carbocyanines ,medicine.disease ,0104 chemical sciences ,Gene Expression Regulation, Neoplastic ,Histone Deacetylase Inhibitors ,010404 medicinal & biomolecular chemistry ,Cancer research ,Heterografts ,Molecular Medicine ,Structure based ,Female ,Histone deacetylase - Abstract
Abnormally high levels of class I histone deacetylases (HDACs) are associated with triple-negative breast cancer (TNBC) proliferation, malignant transformation, and poor prognosis of patients. Herein, we report a near-infrared imaging probe for TNBC detection via visualizing class I HDACs. Conjugating Cy5.5 to a cyclic depsipeptide inhibitor, we obtained the probe (20-Cy5.5) that retained desirable class I HDAC affinity and selectivity. Then, this probe could visualize epigenetic changes by class I HDACs in TNBC MDA-MB-231 cells and in xenograft tumor models in real time. Treatment with suberoylanilide hydroxamic acid (SAHA) significantly reduced the uptake of the probe in tumors, suggesting its potential use in evaluation of therapeutic responses of HDACi-mediated therapy. Moreover, 20-Cy5.5 could detect class I HDAC expression in TNBC lung metastasis. This novel NIR probe that achieves tumor class I HDAC imaging not only leads to a better understanding of epigenetic regulation in tumors but also has great potential for improving the TNBC diagnosis and treatment.
- Published
- 2021