Unknown

Dataset Information

0

Inhibition of Oncogenic Transcription Factor REL by the Natural Product Derivative Calafianin Monomer 101 Induces Proliferation Arrest and Apoptosis in Human B-Lymphoma Cell Lines.


ABSTRACT: Increased activity of transcription factor NF-κB has been implicated in many B-cell lymphomas. We investigated effects of synthetic compound calafianin monomer (CM101) on biochemical and biological properties of NF-κB. In human 293 cells, CM101 selectively inhibited DNA binding by overexpressed NF-κB subunits REL (human c-Rel) and p65 as compared to NF-κB p50, and inhibition of REL and p65 DNA binding by CM101 required a conserved cysteine residue. CM101 also inhibited DNA binding by REL in human B-lymphoma cell lines, and the sensitivity of several B-lymphoma cell lines to CM101-induced proliferation arrest and apoptosis correlated with levels of cellular and nuclear REL. CM101 treatment induced both phosphorylation and decreased expression of anti-apoptotic protein Bcl-XL, a REL target gene product, in sensitive B-lymphoma cell lines. Ectopic expression of Bcl-XL protected SUDHL-2 B-lymphoma cells against CM101-induced apoptosis, and overexpression of a transforming mutant of REL decreased the sensitivity of BJAB B-lymphoma cells to CM101-induced apoptosis. Lipopolysaccharide-induced activation of NF-κB signaling upstream components occurred in RAW264.7 macrophages at CM101 concentrations that blocked NF-κB DNA binding. Direct inhibitors of REL may be useful for treating B-cell lymphomas in which REL is active, and may inhibit B-lymphoma cell growth at doses that do not affect some immune-related responses in normal cells.

SUBMITTER: Yeo AT 

PROVIDER: S-EPMC4863944 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC6822579 | biostudies-literature
| S-EPMC4407428 | biostudies-literature
| S-EPMC4059058 | biostudies-literature
| S-EPMC7118088 | biostudies-literature
| S-EPMC4912327 | biostudies-literature
| S-EPMC4491180 | biostudies-literature
| S-EPMC6678315 | biostudies-literature
| S-EPMC4695110 | biostudies-literature
| S-EPMC2992084 | biostudies-literature
| S-EPMC10466055 | biostudies-literature