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Piperlongumine inhibits proliferation and survival of Burkitt lymphoma in vitro. Leuk Res 2013 Feb;37(2):146-54

Date

12/15/2012

Pubmed ID

23237561

Pubmed Central ID

PMC3551475

DOI

10.1016/j.leukres.2012.11.009

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.

Author List

Han SS, Son DJ, Yun H, Kamberos NL, Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antigens, Differentiation
Antineoplastic Agents
Apoptosis
Burkitt Lymphoma
Caspase 3
Cell Line, Tumor
Cell Proliferation
Cell Survival
Dioxolanes
E2F1 Transcription Factor
Enzyme Activation
Gene Expression Regulation, Neoplastic
Genes, myb
Humans
Inhibitory Concentration 50
NF-kappa B
Proto-Oncogene Proteins c-myc
Viral Matrix Proteins
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc