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Piperlongumine inhibits proliferation and survival of Burkitt lymphoma in vitro
Journal article   Peer reviewed

Piperlongumine inhibits proliferation and survival of Burkitt lymphoma in vitro

Seong-Su Han, Dong-Ju Son, Hwakyung Yun, Natalie L Kamberos and Siegfried Janz
Leukemia research, Vol.37(2), pp.146-154
02/2013
DOI: 10.1016/j.leukres.2012.11.009
PMCID: PMC3551475
PMID: 23237561

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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 (IC50=2.8μM×8.5μM) 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.
Non-Hodgkin lymphoma Long pepper Pyridone alkaloid Cancer therapy and prevention B-cell malignancy

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