| Literature DB >> 22074700 |
Roberto Rosato1, Stefanie Hock, Paul Dent, Yun Dai, Steven Grant.
Abstract
Effects of the HDAC inhibitor LBH-589 (panobinostat) on fludarabine lethality toward acute myeloid leukemia (AML) cells were examined in vitro and in vivo. LBH-589 pretreatment sensitized U937, HL-60, and primary leukemia cells to fludarabine while blocking NF-κB activation accompanied by XIAP down-regulation and JNK activation. Pharmacologic or genetic JNK inhibition significantly attenuated LBH-589/fludarabine lethality, whereas XIAP over-expression diminished JNK activation and apoptosis. Combined in vivo treatment abrogated leukemia growth in a U937 xenograft murine model and substantially increased animal survival. These studies highlight the interplay between NF-κB activation, XIAP down-regulation, and JNK activation in anti-leukemic synergism between fludarabine and LBH-589.Entities:
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Year: 2011 PMID： 22074700 PMCID： PMC3288169 DOI： 10.1016/j.leukres.2011.10.020
Source DB: PubMed Journal: Leuk Res ISSN： 0145-2126 Impact factor: 3.156