title: Piperlongumine inhibits LMP1/MYC-dependent mouse B-lymphoma cells.
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(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.
authors.affiliation: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Seong-Su
authors.initials: SS
authors.lastname: Han
authors.forename: Van S
authors.initials: VS
authors.lastname: Tompkins
authors.forename: Dong-Ju
authors.initials: DJ
authors.lastname: Son
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Kamberos
authors.forename: Laura L
authors.initials: LL
authors.lastname: Stunz
authors.forename: Ahmad
authors.initials: A
authors.lastname: Halwani
authors.forename: Gail A
authors.initials: GA
authors.lastname: Bishop
authors.forename: Siegfried
authors.initials: S
authors.lastname: Janz
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004148:Dioxolanes / Q000494:pharmacology*; D016259:Genes, myc; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000502:physiology*; D010881:Piperidones
chemical_list: D004148:Dioxolanes; D016328:NF-kappa B; D014763:Viral Matrix Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C498077:piperlongumine; D010881:Piperidones
keywords: 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