Cancer cell death strategies by targeting Bcl-2's BH4 domain

Abstract

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Bcl-2 Family of Proteins in the Control of Mitochondrial Calcium Signalling: An Old Chap with New Roles

“…Due to their roles in ER to mitochondria Ca 2+ fluxes described above, anti-apoptotic Bcl-2 proteins have been widely shown to inhibit apoptosis by decreasing ER-induced Ca 2+ release or decreasing VDAC1-dependent Ca 2+ uptake [103] (Figure 1). In recent years, different peptides derived from their BH4 domain have been developed and their effects have been characterized in different cancer cell models [104]. Such peptides are able to disrupt the interactions between IP 3 R and several Bcl-2 proteins and impact on the apoptotic Ca 2+ signals transfer to the mitochondria.…”

Impact of Bupivacaine on malignant proliferation, apoptosis and autophagy of human colorectal cancer SW480 cells through regulating NF-κB signaling path

“…A great many studies have revealed that activating NF-B signaling pathway acts pivotally in the process of CRC cell proliferation, apoptosis, angiogenesis as well as metastasis [ 27 , 28 ]. During activating NF-κB, TLR4 receptor binding to ligand results in activating IKK complex, while IKK activation further promotes IκB phosphorylation, which then triggers the release of NF-κB from nucleus and further stimulates the release of inflammatory factors [ 29 ].…”

The role of Bcl-2 proteins in modulating neuronal Ca2+ signaling in health and in Alzheimer's disease

“…Bcl-2 directly binds to and inhibits the IP 3 R, the major Ca 2+ release channel and an important player in the crosstalk between the ER and mitochondria. This Bcl-2-IP 3 R interaction seems crucial for the inhibition of the IP 3 R-mediated Ca 2+ release from the ER by Bcl-2, and thereby Ca 2+ -mediated apoptosis is prevented [46,81].…”

“…Besides a potential role of Bcl-2"s BH4 domain in controlling Bax activity, the BH4 domain of anti-apoptotic Bcl-2 proteins has mainly emerged as a key determinant to control intracellular Ca 2+ signaling [44,45]. More recently, this BH4 domain also appears an attractive target in anti-cancer strategies, yet ontarget small molecule BH4-domain antagonists ought to emerge [46][47][48].…”