Cytotoxicity of NF-κB inhibitors Bay 11-7085 and caffeic acid phenethyl ester to Ramos and other human B-lymphoma cell lines

Nir Berger, Hannah Ben Bassat, Benjamin Y. Klein, Reuven Laskov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Objective: The viability of normal and malignant B-cells was shown to depend on the constitutive activation of the nuclear factor (NF)- κB pathway. Thus, attempts to find efficient inhibitors of NF-κB play a central role in the search for novel anti-B lymphoma therapies. We studied the effects of two NF-κB inhibitors, Bay 11-7085 (BAY) and caffeic acid phenethyl ester (CAPE), on the viability of B-lymphoma cell lines. Methods: We investigated the mechanism(s) of the cytotoxic effect of the NF-κB inhibitors, BAY, and CAPE on human-lymphoma and nonhematological cell lines. Results: BAY and CAPE were shown to kill Ramos-Burkitt's lymphoma cells with IC50 values of 0.7 μM and 4 μM, respectively. The rapid killing by BAY (h) vs the slower killing by CAPE (1-3 days), and their differential effects on the stages of the cell cycle, indicated that these drugs induce killing by different mechanisms. BAY and CAPE induced a loss of the cytoplasmic compartment and generated pyknotic nuclei, which lacked nuclear or nucleosomal fragmentation, features characteristic of necrosis rather than apoptosis. BAY also induced a rapid loss of the mitochondrial potential and rapid inhibition of p65 NF-κB binding to its κB motif without reducing the level of nuclear p65. Conclusion: Our results indicate that BAY causes a necrotic rather than apoptotic cell death, either through its effect on the NF-κB pathway and/or by affecting additional molecular targets. The high sensitivity of B-lymphoma cell lines to the cytotoxicity of BAY, justify further research to explore its potential therapeutic effect on human B lymphomas.

Original languageEnglish
Pages (from-to)1495-1509
Number of pages15
JournalExperimental Hematology
Volume35
Issue number10
DOIs
StatePublished - Oct 2007

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