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

  • Background
    Advanced cancer has been shown to have a higher percentage of epigenetic changes are more often events than genetic mutations. Preclinical models have showed that combination of the HNHA (N-hydroxy-7-(2-naphthylthio) heptanomide) and 2DG (2-Deoxy-D-glucose) is a play crucial role in ATC (cancer stem-like cell, anaplastic thyroid cancer). The aim of this research is to study that caspase cleavage dependent apoptosis by combination therapy of HNHA and 2DG in ATC.

    Methods
    ATC cell lines were exposed to HNHA and 2DG alone or combined, and cell viability was determined by MTT assay. Synergistic anti-cancer effects of the combination therapy on cell cycle and intracellular signaling pathways were estimated by flow cytometry and immuno blot analysis. The ATC cell lines xenograft model was used to examine the anti-tumor activity in vivo.

    Results
    Consequently, our results are suggest that combination therapy of HNHA and 2DG is synergistically decreased cell viability in ATC cell, and also significantly induced apoptotic cell death in this cells, as showed by the cleavage of caspase-3. HNHA and 2DG combination was reduced anti-apoptotic factor in these cells. Thus, combination therapy with HNHA and 2DG most significantly reduced tumor volume in ATC cell xenografts.

    Discussion & Conclusions
    The current study suggests that HNHA and 2DG combination treatment was more effective than treatment with the HNHA or 2DG alone. These findings may offer a new therapeutic approach to ATC include the cancer stem-like cells.

 

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