Apicidin inhibits cell growth by downregulating IGF-1R in salivary mucoepidermoid carcinoma cells.

Inhibition of histone deacetylases (HDACs) has emerged as a new target for cancer therapies. The present study examined the antitumor effect and molecular mechanism of the HDAC inhibitor apicidin in YD-15 human salivary mucoepidermoid carcinoma (MEC) cells. The cells were treated with apicidin and cell death was quantified using an MTT assay. Apoptosis and autophagy were measured using flow cytometry, immunoblot analysis and cell staining. Regulation of the signaling pathways was monitored using immunoblot analysis and co-treatment with specific inhibitors. Insulin-like growth factor 1 receptor (IGF-1R) was knocked down using specific siRNA. Apicidin significantly inhibited the proliferation of MEC cells. Apicidin also induced apoptosis through the inactivation of extracellular signal-regulated kinase (ERK) and AKT/mTOR signaling and activation of c-Jun NH2-terminal kinase (JNK), whereas apicidin promoted autophagy through inactivation of the AKT/mTOR signaling. These effects may be mediated by the inhibition of IGF-1R, an upstream regulator of MAPK and AKT/mTOR pathways. These results suggested that apicidin is an attractive chemotherapeutic agent against salivary MEC and may be a good candidate for targeting IGF-1R for cancer therapies.