Abstract LB-181: Piperlongumine inhibits growth and survival of human Burkitt lymphoma by downregulating NF-κB, c-Myc and LMP1

Abstract

Abstract Piperlongumine (PL), a natural product constituent of the fruit of the Long pepper, Piper longum, has well documented anti-inflammatory and cancer inhibiting properties. The latter include evidence that PL selectively kills solid tumor cells, but spares their normal counterparts. Because it has not been established whether PL can also inhibit hematological malignancies of the B-lymphocyte lineage, we here decided to evaluate the efficacy with which PL suppresses growth and survival of human non-Hodgkin's Burkitt lymphoma (BL) cells in vitro. We found that PL curbed cell growth (IC50 values of PL for 24h treatment: DG-75; 8.5uM, Daudi; 2.84uM, Raji; 7.7uM and Ramos; 4.5uM) and caused Caspase-3-dependent apoptosis of BL cells in a concentration- and time-dependent manner. PL strongly suppressed constitutive NF-κB signaling by inhibition of IκBα degradation and subsequent nuclear translocation of p65 as well as interruption of NF-κB binding to its consensus DNA sequence. PL also disrupted the expression of NF-κB target genes such as E2F1, c-Myb and GADD45B. c-Myc, transcription factor important for BL development and survival, was remarkably reduced after treatment with PL. In EBV-positive BL cell lines that express high level of LMP1 (e.g., Daudi, Raji), PL efficiently repressed LMP1, a known activator of NF-κB. Considering that NF-κB, c-Myc and LMP1 play important roles in the development and in vivo maintenance of B-lineage and other types of blood cells neoplasms, our findings strongly suggest that PL may afford new approaches to the chemoprevention and treatment of blood cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-181. doi:1538-7445.AM2012-LB-181