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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-08-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558614001031 |
| _version_ | 1818206212469030912 |
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| author | Tao Zhang Yihua Chen Jingjie Li Feifei Yang Haigang Wu Fujun Dai Meichun Hu Xiaoling Lu Yi Peng Mingyao Liu Yongxiang Zhao Zhengfang Yi |
| author_facet | Tao Zhang Yihua Chen Jingjie Li Feifei Yang Haigang Wu Fujun Dai Meichun Hu Xiaoling Lu Yi Peng Mingyao Liu Yongxiang Zhao Zhengfang Yi |
| author_sort | Tao Zhang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T04:09:26Z |
| format | Article |
| id | doaj.art-72268d8a1e0f4a58b6c4ccb6c463195b |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-12T04:09:26Z |
| publishDate | 2014-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-72268d8a1e0f4a58b6c4ccb6c463195b2022-12-22T00:38:40ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022014-08-0116866567710.1016/j.neo.2014.07.009Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast CancerTao Zhang0Yihua Chen1Jingjie Li2Feifei Yang3Haigang Wu4Fujun Dai5Meichun Hu6Xiaoling Lu7Yi Peng8Mingyao Liu9Yongxiang Zhao10Zhengfang Yi11Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, ChinaBiological Targeting Diagnosis and Therapy Research Center, Guangxi Medical University, 22 Shuang Yong Rd. Nanning, Guangxi 530021, ChinaBiological Targeting Diagnosis and Therapy Research Center, Guangxi Medical University, 22 Shuang Yong Rd. Nanning, Guangxi 530021, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, ChinaBiological Targeting Diagnosis and Therapy Research Center, Guangxi Medical University, 22 Shuang Yong Rd. Nanning, Guangxi 530021, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, ChinaAccumulating 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.http://www.sciencedirect.com/science/article/pii/S1476558614001031 |
| spellingShingle | Tao Zhang Yihua Chen Jingjie Li Feifei Yang Haigang Wu Fujun Dai Meichun Hu Xiaoling Lu Yi Peng Mingyao Liu Yongxiang Zhao Zhengfang Yi Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast Cancer Neoplasia: An International Journal for Oncology Research |
| 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 |
| url | http://www.sciencedirect.com/science/article/pii/S1476558614001031 |
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