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Potential anti-cancer activity of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), a histone deacetylase inhibitor, against breast cancer both in vitro and in vivo

Authors
 Ki Cheong Park  ;  Seung Won Kim  ;  Ji Hyun Park  ;  Eun Hye Song  ;  Jeong Won Yang  ;  Hyun Joo Chung  ;  Hye Jin Jung  ;  Jin Suck Suh  ;  Ho Jeong Kwon  ;  Seung Hoon Choi 
Citation
 CANCER SCIENCE, Vol.102(2) : 343-350, 2011 
Journal Title
 CANCER SCIENCE 
ISSN
 1347-9032 
Issue Date
2011
MeSH
Animals ; Antineoplastic Agents/pharmacology* ; Blotting, Western ; Breast Neoplasms/drug therapy* ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Cycle/drug effects ; Cell Proliferation/drug effects ; Cell Separation ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Histone Deacetylase Inhibitors/pharmacology* ; Humans ; Hydroxamic Acids/pharmacology* ; Immunohistochemistry ; Mice ; Naphthalenes/pharmacology* ; Neovascularization, Pathologic/drug therapy ; Xenograft Model Antitumor Assays
Abstract
Histone deacetylase (HDAC) is an attractive target for cancer therapy because it plays a key role in gene expression and carcinogenesis. N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) is a novel synthetic HDAC inhibitor (HDACI) that shows better pharmacological properties than a known HDACI present in the human fibrosarcoma cell: suberoylanilide hydroxamic acid (SAHA). Here, we investigate the anti-cancer activity of HNHA against breast cancer both in vitro and in vivo. HNHA arrested the cell cycle at the G(1) /S phase via p21 induction, which led to profound inhibition of cancer cell growth in vitro. In addition, HNHA-treated cells showed markedly decreased levels of VEGF and HIF-1α than SAHA and fumagillin (FUMA) when accompanied by increased histone acetylation. HNHA significantly inhibited tumor growth in an in vivo mouse xenograft model. HNHA-treated mice survived significantly longer than SAHA- and FUMA-treated mice. Dynamic MRI showed significantly decreased blood flow in the HNHA-treated mice, implying that HNHA inhibits tumor neovascularization. This finding was accompanied by marked reductions of proangiogenic factors and significant induction of angiogenesis inhibitors in tumor tissues. We have shown that HNHA is an effective anti-tumor agent in breast cancer cells in vitro and in breast cancer xenografts in vivo. Collectively, these findings indicate that HNHA may be a potent anti-cancer agent against breast cancer due to its multi-faceted inhibition of HDAC activity, as well as anti-angiogenesis activity.
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2010.01798.x/abstract
DOI
10.1111/j.1349-7006.2010.01798.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Seung Won(김승원) ORCID logo https://orcid.org/0000-0002-1692-1192
Park, Ki Cheong(박기청) ORCID logo https://orcid.org/0000-0002-3435-3985
Park, Ji Hyun(박지현)
Suh, Jin Suck(서진석) ORCID logo https://orcid.org/0000-0001-9455-9240
Song, Eun Hye(송은혜)
Yang, Jeong Won(양정원)
Choi, Seung Hoon(최승훈)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/92615
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