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Title: Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys{sup 38} to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy.
Authors:
 [1] ;  [2] ;  [2] ; ;  [1] ;  [2] ; ;  [1] ;  [2] ;  [2] ;  [3] ;  [1] ;  [2] ;  [2] ; ;  [3] ;  [1] ;  [2] ;  [2] ;  [3] more »;  [4] ; « less
  1. Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China)
  2. (China)
  3. Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China)
  4. Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu (China)
Publication Date:
OSTI Identifier:
22462103
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 462; Journal Issue: 4; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMALS; APOPTOSIS; CELL PROLIFERATION; CURRENTS; DOSES; GENES; INHIBITION; LYMPHOMAS; MUTATIONS; SPECIFICITY; THERAPY