Anaplastic thyroid carcinoma (ATC) and squamous
thyroid carcinoma (STC) are both rare and advanced thyroid
malignancies with a very poor prognosis and an average median survival time of 5 months and less than 20% of affected patients are alive 1 year after diagnosis. The clinical management of both ATC and STC is very similar because they are not particularly responsive to
radiotherapy and
chemotherapy. This inspired us to explore a novel and effective clinically approved
therapy for ATC treatment.
Histone deacetylase inhibitor (HDACi) drugs are recently FDA-approved drug for
malignancies, especially for blood cell
cancers. Therefore, we investigated whether an HDACi drug acts as an effective anticancer drug for advanced
thyroid cancers. Cell viability analysis of
panobinostat treatment demonstrated a significant IC50 of 0.075 µM on SW579 STC cells. In addition,
panobinostat exposure activated
histone acetylation and triggered cell death mainly through cell cycle arrest and apoptosis-related
protein activation. Using CRISPR/Cas9 to knock out HDAC1 and HDAC2 genes in SW579 cells, we observed that the
histone acetylation level and cell cycle arrest were enhanced without any impact on cell growth. Furthermore, HDAC1 and HDAC2 double knockout (KO) cells showed dramatic cell apoptosis activation compared to HDAC1 and HDAC2 individual KO cells. This suggests expressional and biofunctional compensation between HDAC1 and HDAC2 on SW579 cells. This study provides strong evidence that
panobinostat can potentially be used in the clinic of advanced
thyroid cancer patients.