MS275 enhances cytotoxicity induced by 5-fluorouracil in the colorectal cancer cells.
Histone deacetylases (HDACs) activity determines the acetylation status of histons, and has the ability to regulate gene expression through chromatin remodelling. HDACs are a promising target for pharmacological inhibition, since it has been discovered that some genes are repressed by their inappropriate recruitment. To test this we have addressed the hypothesis that histone deacetylase inhibitors SBHA and MS275 potentiate inhibitory effects of classical anti-colorectal cancer cytostatic, 5-fluorouracil (5-FU), on survival of colorectal cancer (CRC) cells in vitro. We are reporting here that HDAC inhibitors show potent synergistic interaction with 5-FU. The observed synergism between HDAC inhibitors and 5-FU is most probably related to the augmented apoptotic signal allowed for significant (both biological and statistical) reduction of the cytotoxic doses.
Department of Pharmacology, National Medicines Institute, Warsaw, Poland. sylwia.flis@yahoo.pl
Sylwia
S
Flis
Agnieszka
A
Gnyszka
Krzysztof
K
Flis
Jacek
J
Spławiński
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011725:Pyridines; C528828:suberoyl bis-hydroxamic acid; C118739:entinostat; D005472:Fluorouracil