title: Antitumor action of a novel histone deacetylase inhibitor, YF479, in breast cancer.
abstract: 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.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
authors.forename: Jingjie
authors.initials: J
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
authors.forename: Haigang
authors.initials: H
authors.lastname: Wu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Dai
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
authors.forename: Meichun
authors.initials: M
authors.lastname: Hu
authors.affiliation: Biological Targeting Diagnosis and Therapy Research Center, Guangxi Medical University, 22 Shuang Yong Rd. Nanning, Guangxi 530021, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Lu
authors.affiliation: Biological Targeting Diagnosis and Therapy Research Center, Guangxi Medical University, 22 Shuang Yong Rd. Nanning, Guangxi 530021, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China; Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030. Electronic address: mliu@ibt.tamhsc.edu.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Biological Targeting Diagnosis and Therapy Research Center, Guangxi Medical University, 22 Shuang Yong Rd. Nanning, Guangxi 530021, China. Electronic address: yongxiangzhao@126.com.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. Electronic address: zfyi@bio.ecnu.edu.cn.
authors.forename: Zhengfang
authors.initials: Z
authors.lastname: Yi
mesh_terms: D000813:Anilides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D062105:Molecular Docking Simulation; D009362:Neoplasm Metastasis; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C000599719:YF479 compound; D006655:Histone Deacetylases