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 ?M × 8.5 ?M) 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-?B and MYC activity, with the former being caused by inhibition of I?B? degradation, nuclear translocation of p65, and binding of NF-?B dimers to cognate DNA sequences in gene promoters. In 4 of 4 BL cell lines, the NF-?B/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-?B, 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.

SUBMITTER: Han SS 

PROVIDER: S-EPMC3551475 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other