The Synergistic Repressive Effect of NF-kappaB and JNK Inhibitor on the Clonogenic Capacity of Jurkat Leukemia Cells Journal Article


Authors: Liu, X; Zhang, J; Li, J; Volk, A; Breslin, P; Zhang, Z
Article Title: The Synergistic Repressive Effect of NF-kappaB and JNK Inhibitor on the Clonogenic Capacity of Jurkat Leukemia Cells
Abstract: Deregulation of Nuclear Transcription Factor-kappaB (NF-kappaB) and Jun N-terminal kinase (JNK) signaling is commonly detected in leukemia, suggesting an important role for these two signaling pathways in the pathogenesis of leukemia. In this study, using Jurkat cells, an acute T-lymphoblastic leukemia (T-ALL) cell line, we evaluated the effects of an NF-kappaB inhibitor and a JNK inhibitor individually and in combination on the proliferation, survival and clonogenic capacity of leukemic cells. We found that leukemic stem/progenitor cells (LSPCs) were more sensitive to NF-kappaB inhibitor treatment than were healthy hematopoietic stem/progenitor cells (HSPCs), as shown by a reduction in the clonogenic capacity of the former. Inactivation of NF-kappaB leads to the activation of JNK signaling in both leukemic cells and healthy HSPCs. Interestingly, JNK inhibitor treatment enhanced the repressive effects of NF-kappaB inhibitor on LSPCs but prevented such repression in HSPCs. Our data suggest that JNK signaling stimulates proliferation/survival in LSPCs but is a death signal in HSPCs. The combination of NF-kappaB inhibitor and JNK inhibitor might provide a better treatment for T-ALL leukemia by synergistically killing LSPCs while simultaneously preventing the death of normal HPCs.
Journal Title: PloS one
Volume: 9
Issue: 12
ISSN: 1932-6203; 1932-6203
Publisher: Unknown  
Date Published: 2014
Start Page: e115490
Language: ENG
DOI/URL:
Notes: LR: 20141220; JID: 101285081; 2014 [ecollection]; 2014/04/11 [received]; 2014/11/24 [accepted]; 2014/12/19 [epublish]; epublish