title: Piperlongumine inhibits proliferation and survival of Burkitt lymphoma in vitro.
abstract: Piperlongumine (PL), a pepper plant alkaloid from Piper longum, kills solid tumor cells in a highly selective, potent fashion. To evaluate whether PL may have similar effects on malignant blood cells, we determined the efficacy with which PL inhibits the B-lymphocyte derived neoplasm, Burkitt lymphoma (BL). Low micromolar concentrations of PL (IC(50) = 2.8 μM × 8.5 μM) curbed growth and survival of two EBV(+) BL cell lines (Daudi, Raji) and two EBV BL cell lines (Ramos, DG-75), but left normal peripheral blood B-lymphocytes unharmed. PL-dependent cytotoxicity was effected in part by reduced NF-κB and MYC activity, with the former being caused by inhibition of IκBα degradation, nuclear translocation of p65, and binding of NF-κB dimers to cognate DNA sequences in gene promoters. In 4 of 4 BL cell lines, the NF-κB/MYC-regulated cellular target genes, E2F1 and MYB, were down regulated, while the stress sensor gene, GADD45B, was up regulated. The EBV-encoded oncogene, LMP-1, was suppressed in Daudi and Raji cells. Considering that NF-κB, MYC and LMP-1 play a crucial role in the biology of many blood cancers including BL, our results provide a strong preclinical rationale for considering PL in new intervention approaches for patients with hematologic malignancies.
authors.affiliation: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Seong-Su
authors.initials: SS
authors.lastname: Han
authors.forename: Dong-Ju
authors.initials: DJ
authors.lastname: Son
authors.forename: Hwakyung
authors.initials: H
authors.lastname: Yun
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Kamberos
authors.forename: Siegfried
authors.initials: S
authors.lastname: Janz
mesh_terms: D000943:Antigens, Differentiation / Q000235:genetics; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004148:Dioxolanes / Q000737:chemistry / Q000494:pharmacology*; D050687:E2F1 Transcription Factor / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020570:Genes, myb; D006801:Humans; D020128:Inhibitory Concentration 50; D016328:NF-kappa B / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics; D000097642:GADD45 Proteins; D010881:Piperidones
chemical_list: D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D053148:Caspase 3; D004148:Dioxolanes; D050687:E2F1 Transcription Factor; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D014763:Viral Matrix Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C086470:GADD45B protein, human; D000097642:GADD45 Proteins; C498077:piperlongumine; D010881:Piperidones