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Biochem Biophys Res Commun. 2013 Jul 12;436(4):660-5. doi: 10.1016/j.bbrc.2013.06.012. Epub 2013 Jun 11.

Piperlongumine inhibits LMP1/MYC-dependent mouse B-lymphoma cells.

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Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.


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(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(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 of PL in new interventions in blood cancers.


BL; Burkitt lymphoma; Cancer therapy and prevention; Epstein Barr virus; NF-κB; PL; Piperlongumine; Transgenic mouse model of human endemic Burkitt lymphoma; p21-Encoding Cdkn1a

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