Histone deacetylase 8 as a novel therapeutic target in oral squamous cell carcinoma.

Abstract

The overexpression of histone deacetylases (HDACs) has been observed in many cancers and inhibition of specific HDAC has emerged as a new target for cancer therapy. The present study examined the expression of HDAC8 and the inhibitory effect of HDAC8 in oral squamous cell carcinoma (OSCC). The expression of HDAC8 was measured in human OSCC tissues and OSCC cell lines using immunohistochemistry and immunoblotting. HDAC8 was knocked down in OSCC cells by transfection with HDAC8 siRNAs and cell proliferation was quantified. Apoptosis and autophagy were measured using flow cytometry and immunoblotting. HDAC8 were overexpressed in OSCC tissues and OSCC cells, mainly localized in the cytoplasm. HDAC8 siRNAs effectively reduced the level of HDAC8 expression and HDAC8 silencing significantly inhibited the proliferation of OSCC cells. HDAC8 knockdown induced apoptotic cell death through caspases activation and pro-survival autophagy in OSCC cells. Combination with HDAC silencing and autophagy inhibition enhanced cell death by increasing apoptosis in OSCC cells. This study suggests that inhibition of HDAC8 might become a novel therapeutic strategy for OSCC.