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Potential anti-cancer effect of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), a novel histone deacetylase inhibitor, for the treatment of thyroid cancer.

 Seok-Mo Kim  ;  Ki-Cheong Park  ;  Jeong-Yong Jeon  ;  Bup-Woo Kim  ;  Hyeung-Kyoo Kim  ;  Ho-Jin Chang  ;  Seung-Hoon Choi  ;  Cheong-Soo Park  ;  Hang-Seok Chang 
 BMC CANCER, Vol.15 : 1003, 2015 
Journal Title
Issue Date
Apoptosis/drug effects ; Calcium/metabolism ; Caspases/metabolism ; Cell Line, Tumor ; Endoplasmic Reticulum/metabolism ; Histone Deacetylase Inhibitors/pharmacology* ; Humans ; Hydroxamic Acids/pharmacology* ; Immunohistochemistry ; Naphthalenes/pharmacology* ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Thyroid Neoplasms/drug therapy* ; Thyroid Neoplasms/metabolism
BACKGROUND: Thyroid cancer has been indicated to have a higher global proportion of DNA methylation and a decreased level of histone acetylation. Previous studies showed that histone gene reviser and epigenetic changes role significant parts in papillary and anaplastic thyroid cancer tumorigenesis. The goal of this research was to study the endoplasmic reticulum (ER) stress-mediated actions of the dominant histone deacetylase (HDAC) inhibitor, N-hydroxy-7-(2-naphthylthio) hepatonomide (HNHA), in thyroid cancer and to explore its effects on apoptotic cell death pathways. METHODS: Experiments were achieved to conclude the effects of HNHA in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) cell lines and xenografts, as compared with two other established HDAC inhibitors (SAHA; suberoylanilide hydroxamic acid and TSA; trichostatin A). RESULTS: Apoptosis, which was induced by all HDAC inhibitors, was particularly significant in HNHA-treated cells, where noticeable B-cell lymphoma-2 (Bcl-2) suppression and caspase activation were observed both in vitro and in vivo. HNHA increased Ca(2+) release from the ER to the cytoplasm. ER stress-dependent apoptosis was induced by HNHA, suggesting that it induced caspase-dependent apoptotic cell death in PTC and ATC. PTC and ATC xenograft studies demonstrated that the antitumor and pro-apoptotic effects of HNHA were greater than those of the established HDAC inhibitors. These HNHA activities reflected its induction of caspase-dependent and ER stress-dependent apoptosis on thyroid cancer cells. CONCLUSIONS: The present study indicated that HNHA possibly provide a new clinical approach to thyroid cancers, including ATC.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Bup Woo(김법우) ORCID logo https://orcid.org/0000-0002-1342-9055
Kim, Seok Mo(김석모) ORCID logo https://orcid.org/0000-0001-8070-0573
Kim, Hyung Kyu(김형규)
Park, Ki Cheong(박기청) ORCID logo https://orcid.org/0000-0002-3435-3985
Park, Cheong Soo(박정수)
Chang, Hang Seok(장항석) ORCID logo https://orcid.org/0000-0002-5162-103X
Jeon, Jeong Yong(전정용)
Choi, Seung Hoon(최승훈)
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