Abstract Title:

Deguelin inhibits expression of IkappaBalpha protein and induces apoptosis of B-CLL cells in vitro.

Abstract Source:

Leukemia. 2007 Aug;21(8):1610-8. Epub 2007 Jun 14. PMID: 17568818

Abstract Author(s):

B Geeraerts, B Vanhoecke, W Vanden Berghe, J Philippé, F Offner, D Deforce

Article Affiliation:

Laboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.

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.

Study Type : In Vitro Study

Print Options


Disqus

Login to Comment

Commenting is limited to Members only. If you are already a member, please login to post a comment. If you do not have a member account and would like to become a member, please click here to begin the process to become a member.