title: Apicidin, a histone deaceylase inhibitor, induces both apoptosis and autophagy in human oral squamous carcinoma cells.
abstract: 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.
authors.affiliation: Department of Pathology, Research Center for Oral Disease Regulation of the Aged, School of Dentistry, Chosun University, Dong-gu, Gwangju 501-759, Republic of Korea.
authors.forename: Mee-Young
authors.initials: MY
authors.lastname: Ahn
authors.forename: Sang-Gun
authors.initials: SG
authors.lastname: Ahn
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Yoon
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D005434:Flow Cytometry; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D015388:Organelles / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D056572:Histone Deacetylase Inhibitors; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D010456:Peptides, Cyclic; C102351:apicidin