Anti-apoptotic BCL-2 family members in development

Abstract

Almost 30 years ago it was first appreciated that anti-apoptotic B-cell lymphoma-2 (BCL-2) prevents the induction of apoptosis not only in malignant cells, but also in normal cellular lineages. This critical observation has rapidly evolved from merely identifying new BCL-2 family members to understanding how their biochemical interactions trigger the cell death process, and, more recently, to pharmacological inhibition of anti-apoptotic BCL-2 function in disease. Indeed, the proper regulation of apoptosis is important in many aspects of life including development, homeostasis, and disease biology. To better understand these processes, scientists have used many tools to assess the contribution of individual anti-apoptotic BCL-2 family members. This review will focus on the prominent roles for BCL-2 and other pro-survival family members in promoting the development of mammals during early embryogenesis, neurogenesis, and hematopoiesis.

Bcl-2 on the brink of breakthroughs in cancer treatment

“…1,2 In this issue of Cell Death and Differentiation, several of the world's leaders in research on Bcl-2 family proteins provide complementary reviews covering multiple facets of this intriguing class of proteins, ranging from cellular and molecular mechanistic insights about how these proteins work and addressing their roles in evolution of programmed cell death mechanisms, mammalian development, cancer genetics, cancer biology and applications towards novel cancer therapies. [3][4][5][6][7][8][9] With the recent approval by FDA of the orally bioavailable and highly selective Bcl-2 inhibitor, venetoclax, for some subtypes of chronic lymphocytic leukemia (CLL), Bcl-2 family proteins are now validated as promising drug targets, with the potential to provide significant advances in the standard of care for patients suffering from oncological maladies and possibly for certain non-oncological diseases as well.…”

“…[4][5][6][7][8][9] The canonical view, shared largely by the authors, envisions that Bax and Bak (proapoptotic proteins that share overall sequence and structural similarity to Bcl-2) oligomerize in the mitochondrial outermembrane to form chains whose ends eventually connect to create lipidic pores that release apoptogenic proteins into the cytosol (cytochrome c, SMAC, Htra2, etc. ), thereby triggering a downstream cascade of cell death protease (caspase) activity.…”

Mechanisms associated to apoptosis of cancer cells by phenolic extracts from two canned common beans varieties (Phaseolus vulgarisL.)

“…The extrinsic pathway begins with external stimuli activating cell death receptors (TNFR and Fas) and their ligands, targeting the pathway to activate caspase 8. Both pathways activate effector caspases 3 and 7 generating cell death (Opferman & Kothari, ).…”

“…The intrinsic pathway can be activated through different stimuli, and is character- the pathway to activate caspase 8. Both pathways activate effector caspases 3 and 7 generating cell death (Opferman & Kothari, 2018 These results can also be associated with the contents of phenolic compounds present in the extracts. Gallic acid present in Negro 8025 is involved in the intrinsic pathway of cell apoptosis, decreasing mitochondrial membrane potential and increasing intracellular reactive oxygen species, activating the pathway of caspase 3 (Dharmendra, Nivedita, & Thomas, 2010).…”

Layer‐by‐layer assembled PLGA nanoparticles carrying miR‐34a cargo inhibit the proliferation and cell cycle progression of triple‐negative breast cancer cells

“…Gene silencing studies demonstrated that LbL NPs carrying miR-34a enabled robust down-regulation of CCND1, MDR1, Notch-1, Survivin, and Bcl-2 (Figure 4), while no silencing was observed for LbL NPs carrying miR-co. Each of these genes plays a critical role in TNBC progression. For example, CCND1 regulates cell cycle progression (Mende et al, 2015), and Bcl-2 is an anti-apoptotic gene that is a reliable prognostic marker for TNBC (Inao et al, 2018;Opferman & Kothari, 2018). These genes, as well as MDR-1, Notch-1, and Survivin all contribute to chemotherapy resistance in TNBC (García-Aranda, Pérez-Ruiz, & Redondo, 2018;Inao et al, 2018;Nestal de Moraes et al, 2015;O'Reilly et al, 2015;Virrey et al, 2008;Zhou et al, 2017).…”