Methods: The effects of SAHA on cell cycle and apoptosis of SAS (a TRAIL resistant human oral cancer cell) was examined using flow cytometry analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, DNA fragmentation assay and Western blotting.
Results: We found SAHA induced apoptosis in human oral cancer cells. Western blotting showed SAHA increased DR5 protein expression and activated caspase-8 and caspase-9. Human recombinant DR5/Fc chimera protein significantly inhibited apoptosis induced by SAHA. Subtoxic concentrations of SAHA sensitize SAS cells to exogenous recombinant TRAIL-induced apoptosis.
Conclusions: These results suggest that SAHA can induce apoptosis through activation of DR5/TRAIL death pathway. Combined treatment of SAHA and TRAIL may be used as a new promising therapy for oral cancer.