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On BH3 Mimetics and Ca2+ Signaling
Pawel E Ferdek1, Monika A Jakubowska1
1Medical Research Council Group, Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, CF10 3AX, United Kingdom.
Drug Development Research
|August 15, 2017
Summary
BH3 mimetics are anticancer drugs that target Bcl-2 proteins. New BH3 mimetics should be tested for effects on cellular calcium (Ca2+) homeostasis before clinical trials.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- BH3 mimetics are anticancer agents that mimic BH3-only proteins.
- They bind to pro-survival Bcl-2 proteins (Bcl-2, Bcl-xL) and disrupt interactions with pro-apoptotic proteins (Bax, Bak).
- Bcl-2 family proteins regulate intracellular calcium (Ca2+) homeostasis.
Purpose of the Study:
- To investigate the effects of BH3 mimetics on cellular Ca2+ homeostasis.
- To highlight the importance of assessing Ca2+ signaling in the development of new BH3 mimetics.
Main Methods:
- Preclinical research involving BH3 mimetics.
- Assessment of intracellular Ca2+ release and fluxes.
- Evaluation of Ca2+ homeostasis disruption.
Main Results:
- Some BH3 mimetics have been reported to release Ca2+ from intracellular stores.
- This release can lead to Ca2+ overload in the cytosol.
- BH3 mimetics can indirectly affect intracellular Ca2+ signals.
Conclusions:
- BH3 mimetics can impact cellular Ca2+ homeostasis.
- Testing the effects of new BH3 mimetics on Ca2+ signaling is crucial.
- This assessment should precede clinical trials to ensure drug safety and efficacy.
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