Synergistic Anti-cancer Effect of Inhibition of Histone Deacetylase and Blockade of the Glycolytic Pathway

Anaplastic Thyroid Cancer (ATC) is characterized by a higher percentage of epigenetic changes; these occur more often than genetic mutations. Studies using preclinical models have reported that a combination of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) and 2-deoxy-D-glucose (2DG) plays a crucial role in cancer stem cell-like cells in ATC. This study aimed to investigate whether combinatorial therapy with HNHA and 2DG promotes tumor suppression via caspase cleavage and cell cycle arrest in ATC. ATC cell lines 8505C and SNU 80, isolated from the current patient, were treated with HNHA and 2DG alone or in combination, and cell viability was determined via the MTT assay. Synergistic anti-cancer effects of combinatorial therapy on the cell cycle and intracellularsignaling pathways were assessed via flow cytometry and immunoblot analyses. An ATC cell line-derived xenograft model was used to examine anti-tumor activity in vivo. Combinatorial therapy with HNHA and 2DG synergistically reduced the viability of ATCcells and significantly induced apoptotic cell death, evident from caspase-3 cleavage. Furthermore, combinatorial therapy downregulated anti-apoptotic factors. Thus, combinatorial therapy significantly suppressed tumor volume in ATC cell xenografts, compared to HNHA or 2DG alone.