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Bcl-2 inhibitors as anti-cancer therapeutics: The impact of and on calcium signaling.
- Source :
-
Cell calcium [Cell Calcium] 2018 Mar; Vol. 70, pp. 102-116. Date of Electronic Publication: 2017 Jun 04. - Publication Year :
- 2018
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Abstract
- Bcl-2-protein family members are essential regulators of apoptosis. Anti-apoptotic Bcl-2 proteins ensure cell survival via different mechanisms, including via binding of pro-apoptotic Bcl-2-family members and the modulation of intracellular Ca <superscript>2+</superscript> -transport systems. Many cancer cells upregulate these proteins to overcome the consequences of ongoing oncogenic stress. Bcl-2 inhibition leading to cell death, therefore emerged as a novel cancer therapy. Different Bcl-2 inhibitors have already been developed including the hydrophobic cleft-targeting BH3 mimetics, which antagonize Bcl-2's ability to scaffold and neutralize pro-apoptotic Bcl-2-family members. As such, the BH3 mimetics have progressed into clinical studies as precision medicines. Furthermore, new inhibitors that target Bcl-2's BH4 domain have been developed as promising anti-cancer tools. Given Bcl-2's role in Ca <superscript>2+</superscript> signaling, these drugs and tools can impact Ca <superscript>2+</superscript> signaling. In addition to this, some Bcl-2 inhibitors may have "off-target" effects that cause Ca <superscript>2+</superscript> -signaling dysregulation not only in cancer cells but also in healthy cells, resulting in adverse effects. In this review, we aim to provide an up-to-date overview of the involvement of intracellular Ca <superscript>2+</superscript> signaling in the working mechanism and "off-target" effects of the different Bcl-2-antagonizing small molecules and peptides.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1532-1991
- Volume :
- 70
- Database :
- MEDLINE
- Journal :
- Cell calcium
- Publication Type :
- Academic Journal
- Accession number :
- 28705421
- Full Text :
- https://doi.org/10.1016/j.ceca.2017.05.014