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Title: Piperlongumine inhibits LMP1/MYC-dependent mouse B-lymphoma cells

Highlights: •Mouse model of human Burkitt lymphoma revealed cancer inhibition by PL. •Treatment with PL led to apoptosis of malignant but not normal B cells. •PL inhibited LMP1–NF-κB–Myc-dependent target genes including p21-encoding Cdkn1a. •PL holds promise for new interventions approaches to hematologic malignancies. -- Abstract: Piperlongumine (PL), isolated from the fruit of Long pepper, Piper longum, is a cancer-inhibiting compound that selectively kills tumor cells while sparing their normal counterparts. Here we evaluated the efficacy with which PL suppresses malignant B cells derived from a newly developed, double-transgenic mouse model of human endemic Burkitt lymphoma (BL), designated mCD40-LMP1/iMyc{sup Eμ}. PL inhibited tumor cell proliferation in a concentration-dependent manner and induced apoptosis of neoplastic but not normal B cells. Treatment with PL resulted in downregulation of EBV-encoded LMP1, cellular Myc, constitutive NF-κB activity, and a host of LMP1-Myc-NF-κB-regulated target genes including Aurka, Bcat1, Bub1b, Ccnb1, Chek1, Fancd2, Tfrc and Xrcc6. Of note, p21{sup Cip1}-encoding Cdkn1a was suppressed independent of changes in Trp53 mRNA levels and p53 DNA-binding activity. Considering the central role of the LMP1–NF-κB–Myc axis in B-lineage neoplasia, these findings further our understanding of the mechanisms by which PL inhibits B-lymphoma and provide a preclinical rationale for the inclusion ofmore » PL in new interventions in blood cancers.« less
Authors:
;  [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [5] ;  [6] ;  [4] ;  [5] ;  [5] ;  [1]
  1. Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA (United States)
  2. Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States)
  3. Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA (United States)
  4. Deparment of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA (United States)
  5. (United States)
  6. Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA (United States)
Publication Date:
OSTI Identifier:
22239664
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 436; Journal Issue: 4; Other Information: Copyright (c) 2013 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; APOPTOSIS; BLOOD; CONCENTRATION RATIO; DNA; FRUITS; GENES; INHIBITION; LYMPHOMAS; MESSENGER-RNA; MONOCLINIC LATTICES; ONCOGENIC VIRUSES; PEPPERS; THERAPY; TRANSGENIC MICE; TUMOR CELLS