Abstract
Preclinical Research 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 Ca(2+) homeostasis, including Ca(2+) release from the intracellular stores as well as Ca(2+) 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 Ca(2+) signals. Indeed, it has been reported that some BH3 mimetics release Ca(2+) from the intracellular stores causing Ca(2+) overload in the cytosol. Therefore, the effects of any new BH3 mimetics on cellular Ca(2+) homeostasis should be tested before these compounds progress to clinical trials. Drug Dev Res 78 : 313-318, 2017. © 2017 Wiley Periodicals, Inc.