| Synergistic Bcl-2 inhibition by ABT-737 and cyclosporine A. | |
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MedLine Citation:
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PMID: 23208368 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Survival of lymphocytes and melanocyte stem cells critically depends on B cell lymphoma 2 (Bcl-2). In T lymphocytes, a basal calcineurin activity maintains Bcl-2 expression in naïve cells, and the activation of the calcineurin pathway orchestrates the regulation of the intrinsic apoptosis pathway after antigen recognition. Therefore, calcineurin inhibitors might potentiate the pro-apoptotic effect of pharmacological Bcl-2 inhibitors on lymphatic cells. In vitro, a reduced Bcl-2 expression in lymphocytes exposed to calcineurin inhibitors increased their sensitivity to the small molecule Bcl-2 inhibitor ABT-737. This correlated with an augmented pro-apoptotic activity of ABT-737 on lymphocytes in combination with cyclosporine A in naïve mice in vivo. Interestingly, similar processes were observed in melanocytes. ABT-737 induced a fur depigmentation at the site of injection, and this effect was expanded to a generalized depigmentation in combination with cyclosporine A. Thus, inhibiting calcineurin increases the pro-apoptotic potency of ABT-737 in cells depending on Bcl-2 for survival. The increased efficacy of Bcl-2 inhibitors in combination with cyclosporine A might be relevant to exploit their anti-neoplastic and immuno-modulatory properties. |
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Authors:
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Pietro E Cippà; Jivko Kamarashev; Jin Chen; Anna K Kraus; Stephan Segerer; Laurence Feldmeyer; Thomas Fehr |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-12-4 |
Journal Detail:
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Title: Apoptosis : an international journal on programmed cell death Volume: - ISSN: 1573-675X ISO Abbreviation: Apoptosis Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9712129 Medline TA: Apoptosis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Institute of Physiology, University of Zürich, Zurich, Switzerland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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