panobinostat and Mouth-Neoplasms

Inhibitors of histone deacetylases (HDACs) represent a novel class of therapeutic anticancer agents. Panobinostat (LBH589) induces apoptosis through the regulation of specificity protein 1 (Sp1) in the oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4. In this study, we analyzed the underlying signaling pathways and the mechanisms involved in this process by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, immunocytochemistry and western blot analysis. LBH589 significantly reduced cell growth and the sub-G1 cell population and induced apoptosis. Sp1 protein expression was significantly reduced following treatment with LBH589 in a concentration-dependent manner. Furthermore, LBH589 upregulated the expression of p27 and p21 and downregulated the expression of cyclin D1, myeloid cell leukemia-1 (Mcl-1) and survivin; this led to the activation of apoptotic signaling pathways through the increase of Bax expression and the decrease of Bid and Bcl-xL expression. Treatment with LBH589 also induced the cleavage of caspase-3 and PARP in the HN22 and HSC4 cells. Taken together, our data demonstrate that LBH589 induces the apoptosis of OSCC cells by suppressing Sp1 expression, indicating that LBH589 may be a promising chemotherapeutic agent for the treatment of OSCC.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Hydroxamic Acids; Indoles; Mouth Neoplasms; Panobinostat; Signal Transduction; Sp1 Transcription Factor; Tetrazolium Salts; Thiazoles