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- Title
Deguelin inhibits expression of IkappaBalpha protein and induces apoptosis of B-CLL cells in vitro.
- Authors
Geeraerts, B.; Vanhoecke, B.; Vanden Berghe, W.; Philippé, J.; Offner, F.; Deforce, D.; Philippé, J
- Abstract
We investigated if deguelin, a naturally occurring rotenoid, was able to inhibit nuclear factor kappa B (NF-kappaB)-binding protein (IkappaBalpha) expression and to induce apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells in vitro. Deguelin-induced cell death in the majority of B-CLL cells and was found to be more toxic toward B-CLL cells than to the normal mononuclear or B-cells, suggesting selectivity towards the malignant cells. Deguelin was found to reduce IkappaBalpha protein expression, and thus interacts with the NFkappaB pathway. The induced apoptosis was characterized by processing of caspase-9 and -3 and poly-(ADP)-ribose-polymerase cleavage. Exposure of B-CLL cells to deguelin resulted in Bcl2-associated protein (Bax) conformational changes and downregulation of the key survival protein myeloid cell leukemia sequence 1 (Mcl-1), which is associated with response to treatment in B-CLL patients. Deguelin retained its ability to induce apoptosis in B-CLL cells in the presence of interleukin-4, a pro-survival cytokine in B-CLL, and when cultured with 50% human serum. These data indicate that deguelin is able to induce apoptosis in B-CLL cells in the presence of pro-survival signals and thus merits further investigation for clinical application either as a single agent or in combination with other anticancer agents.
- Subjects
NF-kappa B; DNA-binding proteins; TRANSCRIPTION factors; LYMPHOCYTIC leukemia; CHRONIC lymphocytic leukemia; INTERLEUKIN-4; BLOOD plasma; APOPTOSIS; CELL physiology; COMPARATIVE studies; INSECTICIDES; INTERLEUKINS; RESEARCH methodology; MEDICAL cooperation; PROTEOLYTIC enzymes; RESEARCH; TRANSFERASES; ISOFLAVONES; EVALUATION research; CASE-control method
- Publication
Leukemia (08876924), 2007, Vol 21, Issue 8, p1610
- ISSN
0887-6924
- Publication type
journal article
- DOI
10.1038/sj.leu.2404788