MDM2 antagonist nutlin-3 displays antiproliferative and proapoptotic activity in mantle cell lymphoma.

ABSTRACT:

Purpose

Mantle cell lymphoma (MCL) has one of the poorest prognoses of the non-Hodgkin's lymphomas, and novel therapeutic approaches are needed. We wished to determine whether Nutlin-3, a novel small-molecule murine double minute 2 (MDM2) antagonist that efficiently activates TP53, might be effective in inducing cell death in MCL.

Experimental design

MCL cell lines with known TP53 status were treated with Nutlin-3, and biological and biochemical consequences were studied. Synergies with the prototypic genotoxic agent doxorubicin and the novel proteasome inhibitor bortezomib were assessed.

Results

Nutlin-3 resulted in a reduction in cell proliferation/viability (IC50 < 10 micromol/L), an increase in the apoptotic fraction, and cell cycle arrest in wild-type (wt) TP53 Z

SUBMITTER: Tabe Y 

PROVIDER: S-EPMC7322626 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature