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

BMC Cancer

Research Article

Jeong-Yong Jeon¹  Ki-Cheong Park²  Bup-Woo Kim²  Seok-Mo Kim²  Hang-Seok Chang²  Cheong-Soo Park²  Seung-Hoon Choi²  Ho-Jin Chang²  Hyeung-Kyoo Kim² 

[1] Department of Nuclear Medicine, Yonsei College of Medicine, 120-752, Seoul, South Korea;Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, 135-720, Gangnam-gu, Seoul, South Korea;

关键词: Thyroid Cancer;    Endoplasmic Reticulum Stress;    Electrophoretic Mobility Shift Assay;    Papillary Thyroid Cancer;    SAHA;   

DOI  :  10.1186/s12885-015-1982-6

 received in 2015-08-18, accepted in 2015-12-08,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThyroid 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.MethodsExperiments 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).ResultsApoptosis, 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 Ca2+ 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.ConclusionsThe present study indicated that HNHA possibly provide a new clinical approach to thyroid cancers, including ATC.

【 授权许可】

CC BY   
© Kim et al. 2015