DHMEQ, a new NF-κB inhibitor, induces apoptosis and enhances fludarabine effects on chronic lymphocytic leukemia cells

Abstract

Chronic lymphocytic leukemia (CLL) is a low-grade lymphoid malignancy incurable with conventional modalities of chemotherapy. Strong and constitutive nuclear factor kappa B (NF-κB) activation is a characteristic of CLL cells. We examined the effects of a new NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on CLL cells. Dehydroxymethylepoxyquinomicin completely abrogated constitutive NF-κB activity and induced apoptosis of CLL cells. Apoptosis induced by DHMEQ was accompanied by downregulation of NF-κB-dependent antiapoptotic genes: c-IAP, Bfl-1, Bcl-XL and c-FLIP. Dehydroxymethylepoxyquinomicin also inhibited NF-κB induced by CD40 and enhanced fludarabine-mediated apoptosis of CLL cells. Results of this study suggest that inhibition of constitutive and inducible NF-κB by DHMEQ in combination with fludarabine is a promising strategy for the treatment of CLL. © 2006 Nature Publishing Group. All rights reserved.