Histone deacetylase inhibitor enhances the anti-leukemic activity of an established nucleoside analogue.
Interest in histone deacetylase (HDAC) inhibitors as antineoplastic agents has been accelerating over the last several years and increasing number of compounds are in or entering clinical trials in humans. Recently, attention has been focused on the ability of HDAC inhibitors to induce perturbations in cell cycle regulatory proteins (e.g. p21CIP1), down regulation of survival signaling pathways (e.g. Raf/MAPkinase/ERK), and disruption of cellular redox state (e.g. reactive oxygen species, ROS). In April 2004 issue of Cancer Research, Maggio et al. report that pre-treatment of human leukemic cells with a histone deacetylase inhibitor, MS-275 significantly enhances the abrogative capacity of an established nucleoside analogue, fludarabine. The study indicates that apart from promoting acetylation of histones and regulation of genes involved in differentiation and apoptosis, MS-275 also induces multiple perturbations in signal transduction, survival and cell cycle regulatory pathways that increase the fludarabine-mediated cell death.
Acharya
Milin R
MR
Department of Pharmaceutics, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, USA.
Figg
William D
WD
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D011725:Pyridines / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D011725:Pyridines; D017382:Reactive Oxygen Species; C118739:entinostat; D004248:DNA (Cytosine-5-)-Methyltransferases; D014740:Vidarabine; C024352:fludarabine