Piperlongumine inhibits proliferation and survival of Burkitt lymphoma in vitro. Leuk Res 2013 Feb;37(2):146-54
Date
12/15/2012Pubmed ID
23237561Pubmed Central ID
PMC3551475DOI
10.1016/j.leukres.2012.11.009Scopus ID
2-s2.0-84872374148 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
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 SAuthor
Siegfried Janz MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antigens, DifferentiationAntineoplastic 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
