Acquired resistance to SAHA is MDR-independent and correlates with losses of histone acetylation, cell cycle arrest and apoptosis

Histone deacetylase inhibitors (HDACi) such as SAHA (suberoylanilide hydroxamic acid) act epigenetically by regulating gene expression through chromatin remodeling. The antineoplastic activity of HDACi is an unquestionable property HDACi. But recent studies have revealed another aspect of HDACi: their association with drug resistance. In particular, resistance acquisition during chemotherapy is a frequent obstacle in cancer treatment. A stable 3-fold SAHA-resistant HCT116/SAHA subline was generated by stepwise exposures of the HCT116 colon tumor cell line to increasing concentrations of SAHA. The acquired SAHA r…