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Synergistic Activity of N-hydroxy-7-(2-naphthylthio) Heptanomide and Sorafenib Against Cancer Stem Cells, Anaplastic Thyroid Cancer

Authors
 Ki Cheong Park  ;  Seok-Mo Kim  ;  Jeong Yong Jeon  ;  Bup-Woo Kim  ;  Hyeung Kyoo Kim  ;  Ho Jin Chang  ;  Yong Sang Lee  ;  Soo Young Kim  ;  Seung Hoon Choi  ;  Cheong Soo Park  ;  Hang-Seok Chang 
Citation
 NEOPLASIA, Vol.19(3) : 145-153, 2017 
Journal Title
 NEOPLASIA 
ISSN
 1522-8002 
Issue Date
2017
Abstract
Anaplastic thyroid carcinoma (ATC) although rare is the most deadly form of thyroid cancer. The fatality rate for ATC is high-pitched, the survival rate at 1 year after diagnosis is <20%. Control of ATC is severely hard and widespread with unpredictability. We Previous proved that histone gene reviser and epigenetic changes role significant parts in papillary and anaplastic thyroid cancer tumorigenesis. Herein, the goal of this study was to investigate the anti-tumor activities of a HDAC inhibitor, HNHA alone and in combination with sorafenib in ATC cells in vitro and in vivo and to explore its effects on apoptotic cell death pathways. Three ATC cell lines were exposed to sorafenib in the presence or absence of HNHA, and cell viability was determined by MTT assay. Effects of combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell lines xenograft model was used to examine the anti-tumor activity in vivo. Our data showed that HNHA and sorafenib synergistically decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as proved by the cleavage of caspase-3 and DNA fragmentation. HNHA and sorafenib combination was reduced anti-apoptotic factor in ATC. Thus, combination therapy with HNHA and sorafenib significantly decreased vessel density, and most significantly reduced tumor volume and increased survival in ATC xenografts. These results propose that HNHA in combination with sorafenib has significant anti-cancer activity in preclinical models, potentially suggesting a new clinical approach for patients of advanced thyroid cancer type.
Files in This Item:
T201701033.pdf Download
DOI
10.1016/j.neo.2016.12.005
Appears in Collections:
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, Soo Young(김수영) ORCID logo https://orcid.org/0000-0002-8919-3456
Kim, Hyung Kyu(김형규)
Park, Ki Cheong(박기청) ORCID logo https://orcid.org/0000-0002-3435-3985
Park, Cheong Soo(박정수)
Lee, Yong Sang(이용상) ORCID logo https://orcid.org/0000-0002-8234-8718
Chang, Hang Seok(장항석) ORCID logo https://orcid.org/0000-0002-5162-103X
Jeon, Jeong Yong(전정용)
Choi, Seung Hoon(최승훈)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154565
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