The synergistic repressive effect of NF-κB and JNK inhibitor on the clonogenic capacity of Jurkat leukemia cells.
Deregulation of Nuclear Transcription Factor-κB (NF-κB) 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-A...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0115490&type=printable |
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| _version_ | 1850190561781219328 |
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| author | Xinli Liu Jun Zhang Jing Li Andrew Volk Peter Breslin Jiwang Zhang Zhou Zhang |
| author_facet | Xinli Liu Jun Zhang Jing Li Andrew Volk Peter Breslin Jiwang Zhang Zhou Zhang |
| author_sort | Xinli Liu |
| collection | DOAJ |
| description | Deregulation of Nuclear Transcription Factor-κB (NF-κB) 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-κB 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-κB 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-κB leads to the activation of JNK signaling in both leukemic cells and healthy HSPCs. Interestingly, JNK inhibitor treatment enhanced the repressive effects of NF-κB 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-κB 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. |
| format | Article |
| id | doaj-art-455cf2c736d449eb836c82f67c759f30 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-455cf2c736d449eb836c82f67c759f302025-08-20T02:15:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11549010.1371/journal.pone.0115490The synergistic repressive effect of NF-κB and JNK inhibitor on the clonogenic capacity of Jurkat leukemia cells.Xinli LiuJun ZhangJing LiAndrew VolkPeter BreslinJiwang ZhangZhou ZhangDeregulation of Nuclear Transcription Factor-κB (NF-κB) 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-κB 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-κB 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-κB leads to the activation of JNK signaling in both leukemic cells and healthy HSPCs. Interestingly, JNK inhibitor treatment enhanced the repressive effects of NF-κB 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-κB 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0115490&type=printable |
| spellingShingle | Xinli Liu Jun Zhang Jing Li Andrew Volk Peter Breslin Jiwang Zhang Zhou Zhang The synergistic repressive effect of NF-κB and JNK inhibitor on the clonogenic capacity of Jurkat leukemia cells. PLoS ONE |
| title | The synergistic repressive effect of NF-κB and JNK inhibitor on the clonogenic capacity of Jurkat leukemia cells. |
| title_full | The synergistic repressive effect of NF-κB and JNK inhibitor on the clonogenic capacity of Jurkat leukemia cells. |
| title_fullStr | The synergistic repressive effect of NF-κB and JNK inhibitor on the clonogenic capacity of Jurkat leukemia cells. |
| title_full_unstemmed | The synergistic repressive effect of NF-κB and JNK inhibitor on the clonogenic capacity of Jurkat leukemia cells. |
| title_short | The synergistic repressive effect of NF-κB and JNK inhibitor on the clonogenic capacity of Jurkat leukemia cells. |
| title_sort | synergistic repressive effect of nf κb and jnk inhibitor on the clonogenic capacity of jurkat leukemia cells |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0115490&type=printable |
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