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 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.