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

Leukemia
Ryouichi HorieK Umezawa

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-kappaB) activation is a characteristic of CLL cells. We examined the effects of a new NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on CLL cells. Dehydroxymethylepoxyquinomicin completely abrogated constitutive NF-kappaB activity and induced apoptosis of CLL cells. Apoptosis induced by DHMEQ was accompanied by downregulation of NF-kappaB-dependent antiapoptotic genes: c-IAP, Bfl-1, Bcl-X(L) and c-FLIP. Dehydroxymethylepoxyquinomicin also inhibited NF-kappaB induced by CD40 and enhanced fludarabine-mediated apoptosis of CLL cells. Results of this study suggest that inhibition of constitutive and inducible NF-kappaB by DHMEQ in combination with fludarabine is a promising strategy for the treatment of CLL.

References

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Citations

Sep 24, 2013·Apoptosis : an International Journal on Programmed Cell Death·Ju-Yoon YoonSpencer B Gibson
Dec 1, 2009·Future Medicinal Chemistry·Samedy OukHsiou-Chi Liou
Feb 13, 2010·Expert Opinion on Therapeutic Targets·Monica Lopez-Guerra, Dolors Colomer
Feb 12, 2009·International Journal of Laboratory Hematology·O BaireyO Shpilberg
Jan 8, 2015·Cellular Oncology (Dordrecht)·Mohammad ShahjahaniNajmaldin Saki
Dec 18, 2013·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Tomiteru ToganoRyouichi Horie
Sep 8, 2016·Clinical Lymphoma, Myeloma & Leukemia·Suliman A AlsagabyChris Pepper
Sep 26, 2009·Biochemical and Biophysical Research Communications·Tomiteru ToganoRyouichi Horie
Nov 24, 2011·The American Journal of Pathology·Mariko WatanabeRyouichi Horie
May 10, 2020·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·M F CandidoMaría Sol Brassesco
Dec 27, 2013·Journal of Clinical and Experimental Hematopathology : JCEH·Ryouichi Horie
Apr 9, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mónica López-GuerraDolors Colomer
Jan 2, 2019·Analytica Chimica Acta·Bingzhi LiXuemin Zhou

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