Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import.
Biochem Biophys Res Commun
; 462(4): 326-31, 2015 Jul 10.
Article
in En
| MEDLINE
| ID: mdl-25979358
ABSTRACT
Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys(38) to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Cell Nucleus
/
Lymphoma, Large B-Cell, Diffuse
/
Dioxolanes
/
Transcription Factor RelA
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Year:
2015
Type:
Article