HDAC inhibitors, MS275 and SBHA, enhances cytotoxicity induced by oxaliplatin in the colorectal cancer cell lines.
Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression by catalyzing the removal of acetyl groups, stimulating chromatin condensation, and promoting transcriptional repression. Since aberrant epigenetic changes are a hallmark of cancer, HDACs appear a promising target for pharmacological inhibition. To test this we have addressed the hypothesis that histone deacetylase inhibitors (HDACi), MS275 and SBHA, potentiate inhibitory effects of classical anti-colorectal cancer cytostatic, oxaliplatin, on survival of colorectal cancer (CRC) cells in vitro. We are reporting here that HDACi shows potent synergistic interaction with oxaliplatin. The observed synergism between HDACi and oxaliplatin is most probably related to the augmented apoptotic signal and allowed for significant reduction of doses of anticancer agents used.
Flis
Sylwia
S
Department of Pharmacology, National Medicines Institute, Warsaw, Poland. sylwia.flis@yahoo.pl
Gnyszka
Agnieszka
A
Spławiński
Jacek
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001549:Benzamides / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D011725:Pyridines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009944:Organoplatinum Compounds; D011725:Pyridines; C528828:suberoyl bis-hydroxamic acid; D000077150:Oxaliplatin; C118739:entinostat