apicidin and Mouth-Neoplasms

Apicidin acts as a potent histone deacetylases (HDAC) inhibitor and the precise mechanism for its anti-tumor activity in human oral squamous cell carcinoma (OSCC) cells has not been examined. The aim of this study was to evaluate the anti-tumor efficacy of apicidin through apoptosis and autophagy in OSCC cells. Cells were treated with apicidin and cell death was quantified. Cell cycle and apoptosis were measured using flow cytometry assay, immunoblot. Autophagy was characterized by the increase of LC3B-II and the formation of acidic vesicular organelles (AVOs). Apicidin significantly inhibited the proliferation of OSCC cells in a dose-dependent manner. Apicidin markedly up-regulated p21(WAF1) led to G2/M phase arrest. Apicidin significantly increased the number of apoptotic cells compared to untreated control. Apicidin induced not only apoptosis but also autophagy in OSCC cells. Apicidin dramatically increased the levels of LC3 type II expression, ATG5 protein expression and the accumulation of AVOs. Inhibition of autophagy enhanced apicidin-mediated cytotoxicity through an increase in apoptosis. These results suggest that apicidin exerts anti-tumor effects by inducing apoptosis and autophagy and provide novel evidence of apicidin-induced autophagy and autophagy inhibition enhances apicidin-mediated apoptosis in OSCC cells.

Topics: Apoptosis; Autophagy; Autophagy-Related Protein 5; Blotting, Western; Carcinoma, Squamous Cell; Cell Cycle; Flow Cytometry; Histone Deacetylase Inhibitors; Humans; Microtubule-Associated Proteins; Mouth Neoplasms; Organelles; Peptides, Cyclic; Up-Regulation