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Introduction to Cancer, Conventional Therapies, and Bionano-Based Advanced Anticancer Strategies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Necrosis is a death mechanism, in which cells die accidently in response to an acute insult such as snake biting, trauma or lack of blood supply, etc. In the case of necrosis, the cells undergo plasma membrane permeabilization, swelling, and rupture, and by that the necrotic cells spill out the cellular contents over their neighbors, which invite the damage associated molecular patterns (DAMPs) and may initiate inflammation. Necrosis is also termed as necroptosis and it is mediated by death receptor TNFR1 (tumor necrosis factor receptor). On TNF stimulation, TNFR1 goes through a confirmation change and recruits TNFR-associated death domain protein (TRADD), TRARF2, cellular inhibitor of apoptosis protein 1 (cIAP1), cIAP2, and receptor interacting protein kinase 1 (RIPK1), to form complex 1. RIPK1 is polyubiquinated by cIPA1 and c1PA2 activates NFkB. Caspase 8 cleavage induces apoptosis, in certain condition, and caspase 8 inhibition will induce necroptosis. Necroptosis involves several factors such as ROS production, lysosomal permeabalization, AIF release, and PARP activation. When caspase activation is not involved, necroptosis is associated with the formation of autophagic vesicles.
Apoptosis of Biliary Epithelial Cells
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Natalie J. Török, Gregory J. Gores
Caspase 8 is the initiator caspase in the death-receptor pathway. After the ligands bind to the death receptors such as CD95 (Apol-Fas), TNF-α (TNF-α receptor) or TRAIL-ligand (TRAIL-receptor), aggregation, and formation of membrane-bound signaling complexes occur. These complexes then recruit several molecules of pro-caspase 8, and the resulting high concentration of the enzyme results in auto-activation.5 Once caspase 8 is activated, it cleaves cytosolic Bid, a proapoptotic Bcl-2 family member. The carboxyl fragment of Bid translocates to the mitochondria, where it induces cytochrome c release. Downstream effector caspases are then activated and cell death occurs. Caspase 8 may bypass the mitochondrial requirement in some cells such as lymphocytes,6 by direcdy cleaving caspase 3. Mitochondria, however, substantially amplify the caspase 8-induced cascade.
Cell-mediated immunity
Published in Gabriel Virella, Medical Immunology, 2019
José C. Crispín, Gabriel Virella
A second pathway through which CD8 T cells can induce apoptosis in target cells is mediated by membrane-bound molecules such as FasL. FasL binds to Fas (CD95) and promotes the assembly of a death-inducing signaling complex in the Fas-bearing cell. The activation of this pathway is associated with activation of caspase 8, which in turn will trigger the cascade that leads to activation of effector caspases and apoptosis. These two pathways are not mutually exclusive. In fact, there is data that suggest that activation of both pathways is required in vivo for efficient cytotoxicity.
A patent review of NLRP3 inhibitors to treat autoimmune diseases
Published in Expert Opinion on Therapeutic Patents, 2023
Yiming Xu, Savannah Biby, Baljit Kaur, Shijun Zhang
The activation of the NLRP3 inflammasome via the alternative pathway is observed in human and porcine monocytes but not in murine monocytes (Figure 2) [40]. Upon stimulation with LPS, TLR4 activates myeloid differentiation primary response 88 (MyD88) and Toll/IL-1 R (TIR)-domain-containing adapter-inducing interferon-β (TRIF), leading to the activation of the NF-κB pathway, and the formation of a complex comprising receptor-interacting serine/threonine protein kinase 1 (RIPK1) and FAS-associated death domain protein (FADD). This complex then triggers the activation of caspase-8, ultimately leading to the activation of the NLRP3 inflammasome. In the TRIF-RIPK1-FADD-caspase 8 cascade, the events observed under canonical NLRP3 inflammasome activation, such as ASC speck formation, K+ efflux, GSDMD cleavage, and pyroptosis, are typically dispensable [40].
Effects of radiofrequency radiation on apoptotic and antiapoptotic factors in colorectal cancer cells
Published in Electromagnetic Biology and Medicine, 2022
Sanem Gökçen, Berrak Kurt, Yusuf Küçükbağrıaçık, Elcin Ozgur-Buyukatalay, Görkem Kismali
The immune system destroys defective cells by apoptosis, but cancer cells can develop defense mechanisms by increasing resistance to apoptosis. Inducing apoptosis is a new therapeutic target for cancer cells (Bremer et al. 2006). Members of the BCL-2 family play an important role in deciding whether a cell will survive in the event of cellular damage. BCL-2 family members are anti-apoptotic proteins like BCL-2, BCL-XL, pro-apoptotic like BCL-W BAX, BAK, BCL-XS (Adams and Cory 2001; Gross et al. 1999). Survivin is a member of the inhibitor family of apoptosis proteins (IAP) and is often indicated in cancer cell lines. Members of the human IAP family proteins XIAP, c-IAP1 and c-IAP2 are involved in the inhibition of caspases 3, 7, and 9, while survivin is involved in the inhibition of caspase 3 and 7 (Suzuki et al. 2001). Caspase-8 plays a role in suppressing cellular necrosis and regulating auto-phage and increasing cellular adhesion. Defects in the role of caspase-8 can cause tumor development and progression (Graf et al. 2014).
Effects of smokeless tobacco on cell viability, reactive oxygen species, apoptosis, and inflammatory cytokines in human umbilical vein endothelial cells
Published in Toxicology Mechanisms and Methods, 2021
Junwei Zhao, Liangjun Qiao, Pingping Shang, Chenfeng Hua, Yuming Xie, Xiang Li, Meizhou Ding, Kejian Liu, Junwei Guo, Ge Zhao, Sheng Wang, Huimin Liu, Fuwei Xie
Previous results stated that smokeless tobacco extract may cause apoptosis in multiple cell types (Mangipudy and Vishwanatha 1999; Li et al. 2018). For example, a previous study (Lombard et al. 2010) demonstrated that smokeless tobacco-induced cell death in human macrophages was mediated through the induction of apoptosis. Results from this study showed that snus extracts could cause apoptosis and DNA damage in HUVECs. Modest early apoptosis was observed, and the apoptosis-related gene expression was changed as well. Caspase-8 has been intensely studied as a critical initiator of the extrinsic apoptosis pathway (Yan et al. 2006; Lombard et al. 2010). In the current study, we demonstrated that snus DMSO extracts could activate the cleavage of caspase-8, and the expression of FAS and FADD, extrinsic pathway related genes, were upregulated as well. Moreover, the BAX/BCL-2 ratio increased in cells exposed to conventional cigarette smoke rather than snus extracts. These results suggested that the apoptosis induced by snus extracts mainly depended on the intrinsic and extrinsic pathways. We noticed that TP53 expression was not changed in any treated group as well, which indicated that apoptosis induced by snus extracts was p53-independent. The future work could investigate how the smokeless tobacco induces apoptosis by extrinsic pathway and the detailed mechanisms of related cell death.