On BH3 Mimetics and Ca2+ Signaling

ABSTRACT BH3 mimetics are anticancer agents that reproduce the spatial arrangement of the BH3 domain of Bcl‐2 family proteins. Just like the BH3‐only proteins, these compounds bind to the hydrophobic cleft of the pro‐survival Bcl‐2 members such as Bcl‐2 or Bcl‐xL, and disrupt their heterodimerization with pro‐apoptotic Bax or Bak, sensitizing cells to chemotherapy. In recent years, it has become clear that Bcl‐2 family proteins are engaged in regulation of intracellular Ca2+ homeostasis, including Ca2+ release from the intracellular stores as well as Ca2+ fluxes across the plasma membrane. Given that BH3 mimetics shift the balance between the prosurvival and proapoptotic Bcl‐2 members, they might indirectly exert effects on intracellular Ca2+ signals. Indeed, it has been reported that some BH3 mimetics release Ca2+ from the intracellular stores causing Ca2+ overload in the cytosol. Therefore, the effects of any new BH3 mimetics on cellular Ca2+ homeostasis should be tested before these compounds progress to clinical trials. Drug Dev Res, 2017. © 2017 The Authors Drug Development Research Published by Wiley Periodicals, Inc.
Source: Drug Development Research - Category: Drugs & Pharmacology Authors: Tags: Research Commentary Source Type: research