کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2137512 | 1087847 | 2012 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: LBH-589 (panobinostat) potentiates fludarabine anti-leukemic activity through a JNK- and XIAP-dependent mechanism LBH-589 (panobinostat) potentiates fludarabine anti-leukemic activity through a JNK- and XIAP-dependent mechanism](/preview/png/2137512.png)
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.
Journal: Leukemia Research - Volume 36, Issue 4, April 2012, Pages 491–498