PTEN/AKT pathway involved in histone deacetylases inhibitor induced cell growth inhibition and apoptosis of oral squamous cell carcinoma cells

Histone deacetylases (HDACs) inhibitors induce cell growth arrest and apoptosis in a wide variety of tumor cells. The purpose of this study was to evaluate the effects of trichostatin A (TSA), one of the HDACs inhibitors, on proliferation and apoptosis of oral squamous cell carcinoma cells. Exposure of Tca83 cells (established from human tongue squamous cell carcinoma) to TSA resulted in cell growth inhibition and apoptosis in a dose-dependent manner as measured with MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and DAPI (4'6'diamidino-2-phenylindole dihydrochloride) staining. Western blot showed that both total PTEN and membrane-bound PTEN were induced by TSA treatment, whereas phosphorylation level (Ser 473) of AKT was correspondingly down-regulated by TSA treatment. Knock-down of PTEN expression with PTEN siRNA could sufficiently block 0.25 mu g/ml TSA induced inhibition of cell growth, but failed to block 0.5 mu g/ml TSA induced inhibition of cell growth and apoptosis. Moreover, induction of apoptosis by TSA treatment was also demonstrated by cytochrome C releasing and induction of caspase-3. Conclusively, the results suggested that PTEN/AKT pathway was involved in TSA induced cell growth inhibition and apoptosis of oral squamous cell carcinoma cells. HDACs inhibitors could be potential anticancer drugs for chemotherapy of oral squamous cell carcinoma. (C) 2009 Elsevier Ltd. All rights reserved.