title: Synergistic Activity of N-hydroxy-7-(2-naphthylthio) Heptanomide and Sorafenib Against Cancer Stem Cells, Anaplastic Thyroid Cancer.
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.
authors.affiliation: Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Ki Cheong
authors.initials: KC
authors.lastname: Park
authors.affiliation: Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Seok-Mo
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Yonsei College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Jeong Yong
authors.initials: JY
authors.lastname: Jeon
authors.affiliation: Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Bup-Woo
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Hyeung Kyoo
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Chang
authors.affiliation: Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Cheong Soo
authors.initials: CS
authors.lastname: Park
authors.affiliation: Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea; Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea. Electronic address: SURGHSC@yuhs.ac.
authors.forename: Hang-Seok
authors.initials: HS
authors.lastname: Chang