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Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast Cancer()

Accumulating evidence demonstrates important roles for histone deacetylase in tumorigenesis (HDACs), highlighting them as attractive targets for antitumor drug development. Histone deactylase inhibitors (HDACIs), which have shown favorable anti-tumor activity with low toxicity in clinical investigat...

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Autores principales: Zhang, Tao, Chen, Yihua, Li, Jingjie, Yang, Feifei, Wu, Haigang, Dai, Fujun, Hu, Meichun, Lu, Xiaoling, Peng, Yi, Liu, Mingyao, Zhao, Yongxiang, Yi, Zhengfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234873/
https://www.ncbi.nlm.nih.gov/pubmed/25220594
http://dx.doi.org/10.1016/j.neo.2014.07.009
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author Zhang, Tao
Chen, Yihua
Li, Jingjie
Yang, Feifei
Wu, Haigang
Dai, Fujun
Hu, Meichun
Lu, Xiaoling
Peng, Yi
Liu, Mingyao
Zhao, Yongxiang
Yi, Zhengfang
author_facet Zhang, Tao
Chen, Yihua
Li, Jingjie
Yang, Feifei
Wu, Haigang
Dai, Fujun
Hu, Meichun
Lu, Xiaoling
Peng, Yi
Liu, Mingyao
Zhao, Yongxiang
Yi, Zhengfang
author_sort Zhang, Tao
collection PubMed
description Accumulating evidence demonstrates important roles for histone deacetylase in tumorigenesis (HDACs), highlighting them as attractive targets for antitumor drug development. Histone deactylase inhibitors (HDACIs), which have shown favorable anti-tumor activity with low toxicity in clinical investigations, are a promising class of anticancer therapeutics. Here, we screened our compound library to explore small molecules that possess anti-HDAC activity and identified a novel HDACI, YF479. Suberoylanilide hydroxamic acid (SAHA), which was the first approved HDAC inhibitor for clinical treatment by the FDA, was as positive control in our experiments. We further demonstrated YF479 abated cell viability, suppressed colony formation and tumor cell motility in vitro. To investigate YF479 with superior pharmacodynamic properties, we developed spontaneous and experimental breast cancer animal models. Our results showed YF479 significantly inhibited breast tumor growth and metastasis in vivo. Further study indicated YF479 suppressed both early and end stages of metastatic progression. Subsequent adjuvant chemotherapy animal experiment revealed the elimination of local-regional recurrence (LRR) and distant metastasis by YF479. More important, YF479 remarkably prolonged the survival of tumor-bearing mice. Intriguingly, YF479 displayed more potent anti-tumor activity in vitro and in vivo compared with SAHA. Together, our results suggest that YF479, a novel HDACI, inhibits breast tumor growth, metastasis and recurrence. In light of these results, YF479 may be an effective therapeutic option in clinical trials for patients burdened by breast cancer.
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spelling pubmed-42348732014-11-18 Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast Cancer() Zhang, Tao Chen, Yihua Li, Jingjie Yang, Feifei Wu, Haigang Dai, Fujun Hu, Meichun Lu, Xiaoling Peng, Yi Liu, Mingyao Zhao, Yongxiang Yi, Zhengfang Neoplasia Article Accumulating evidence demonstrates important roles for histone deacetylase in tumorigenesis (HDACs), highlighting them as attractive targets for antitumor drug development. Histone deactylase inhibitors (HDACIs), which have shown favorable anti-tumor activity with low toxicity in clinical investigations, are a promising class of anticancer therapeutics. Here, we screened our compound library to explore small molecules that possess anti-HDAC activity and identified a novel HDACI, YF479. Suberoylanilide hydroxamic acid (SAHA), which was the first approved HDAC inhibitor for clinical treatment by the FDA, was as positive control in our experiments. We further demonstrated YF479 abated cell viability, suppressed colony formation and tumor cell motility in vitro. To investigate YF479 with superior pharmacodynamic properties, we developed spontaneous and experimental breast cancer animal models. Our results showed YF479 significantly inhibited breast tumor growth and metastasis in vivo. Further study indicated YF479 suppressed both early and end stages of metastatic progression. Subsequent adjuvant chemotherapy animal experiment revealed the elimination of local-regional recurrence (LRR) and distant metastasis by YF479. More important, YF479 remarkably prolonged the survival of tumor-bearing mice. Intriguingly, YF479 displayed more potent anti-tumor activity in vitro and in vivo compared with SAHA. Together, our results suggest that YF479, a novel HDACI, inhibits breast tumor growth, metastasis and recurrence. In light of these results, YF479 may be an effective therapeutic option in clinical trials for patients burdened by breast cancer. Neoplasia Press 2014-09-10 /pmc/articles/PMC4234873/ /pubmed/25220594 http://dx.doi.org/10.1016/j.neo.2014.07.009 Text en © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Zhang, Tao
Chen, Yihua
Li, Jingjie
Yang, Feifei
Wu, Haigang
Dai, Fujun
Hu, Meichun
Lu, Xiaoling
Peng, Yi
Liu, Mingyao
Zhao, Yongxiang
Yi, Zhengfang
Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast Cancer()
title Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast Cancer()
title_full Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast Cancer()
title_fullStr Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast Cancer()
title_full_unstemmed Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast Cancer()
title_short Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast Cancer()
title_sort antitumor action of a novel histone deacetylase inhibitor, yf479, in breast cancer()
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234873/
https://www.ncbi.nlm.nih.gov/pubmed/25220594
http://dx.doi.org/10.1016/j.neo.2014.07.009
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