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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.
The Silver Lining
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Mark R Frey, Misty Good, Steven J. McElroy
In contrast to apoptosis, cells undergoing necroptosis (53, 54) show morphological features similar to necrosis, but the mechanism involves specific signaling requiring kinase activity of receptor-interacting proteins (RIPs). In some cases, necroptosis seems to serve as a “backstop” programmed death pathway when pro-apoptotic signals are present but caspases are inhibited (55). The involvement of necroptosis in intestinal inflammation is an emerging field (56), and its role, if any, in NEC remains unknown.
The Role of Nanoparticles in Cancer Therapy through Apoptosis Induction
Published in Hala Gali-Muhtasib, Racha Chouaib, Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Marveh Rahmati, Saeid Amanpour, Hadiseh Mohammadpour
Two important molecular events that are exclusively considered as apoptosis hallmarks are (1) the externalization of phosphatidylserine and (2) activation of the caspase family of proteins [16, 18]. The morphological features of apoptosis are also different from necrosis [19, 20]. Apoptotic cells typically manifest extensive membrane blebbing, shrinkage of the cell, and nuclear condensation and fragmentation; while necrotic cells show membrane disruption, cell swelling, and decondensation of nuclei [19, 20]. However, recent reports have described a form of regulated necrosis, which is initiated via the activation of apoptotic cell signaling, but terminated with necrosis features [19]. Necroptosis is activated in response to the members of the “death receptor” subset of the TNF superfamily, without caspase activation. Necroptosis occurs in cells that express the kinase, RIPK3 to RIPK1. In a normal situation, CASP-8 suppresses the activation of RIPK3 onto RIPK1, and necroptosis is activated, followed by an infection with some viruses having caspase inhibitors. The most important difference between necroptosis and other types of cell death is the involvement of RIPK3/RIPK1 and the absence of caspase activity [21, 22].
A novel necroptosis-related gene signature in acute myeloid leukemia
Published in Hematology, 2023
Weiyue Fang, Hongdou Lin, Junyi Chen, Wenjian Guo
Necroptosis is a newly identified type of programmed cell death that can be activated in the absence of apoptosis and triggered by the activation of death receptors [3]. Emerging studies indicate that receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3) and downstream substrate pseudokinase mixed-lineage kinase domain-like (MLKL) play a crucial role in regulating necroptosis pathway [4]. The effects of necroptosis on cancer can be complex and paradoxical. On the one hand, many pivotal molecules in necroptotic signaling are downregulated in different types of cancer, such as breast cancer, colorectal cancer [5,6]. In this way, cancer cells may evade necroptosis and maintain proliferation. This suggests that necroptosis might help eliminate antiapoptotic tumor cells [7]. On the other hand, an increasing number of studies have also shown that necroptosis can promote tumor progression and metastasis by inducing an inflammatory response and creating a tumor-promoting microenvironment with elevated ROS production [8]. These changes in the tumor microenvironment can lead to genomic instability, ultimately accelerating malignant transformation [9,10].
Development of neoantigens: from identification in cancer cells to application in cancer vaccines
Published in Expert Review of Vaccines, 2022
Nasim Ebrahimi, Maryam Akbari, Masoud Ghanaatian, Parichehr Roozbahani moghaddam, Samaneh Adelian, Marziyeh Borjian Boroujeni, Elnaz Yazdani, Amirhossein Ahmadi, Michael R. Hamblin
Necroptosis is an alternative mode of programmed cell death with features of both apoptosis and necrosis. In a similar manner to necrosis, it is considered to be pro-inflammatory, but is more effective in triggering the maturation of dendritic cells, cross-priming of cytotoxic T cells, and the secretion of IFN-gamma. This leads to better sensitization to tumor antigens contained within the necroptotic cancer cells [118]. Aaes et al. developed a method to produce necroptotic cells using direct dimerization of FADD combined with inducible expression of RIPK3 (receptor interacting protein kinase-3). These necroptotic cells enabled successful prophylactic vaccination of mice against CT26 colorectal tumors [118]. In another study by Turubanova et al. they used photodynamic therapy (PDT) mediated by two different photosensitizers, Photosens (PS) and Photodithazine (PD) against murine glioma GL261 and fibrosarcoma MCA205 cells. The type of cell death induced was analyzed by flow cytometry. The results indicated that PDT with PS or PD were novel ICD inducers, and could be used as a potential approach to prepare cancer vaccines [119].
Association between serum sFasL concentrations and sepsis mortality
Published in Infectious Diseases, 2021
Leonardo Lorente, María M. Martín, Raquel Ortiz-López, Agustín F. González-Rivero, Antonia Pérez-Cejas, Judith Cabrera, Carolina García, Luis Uribe, Alejandro Jiménez
The sFasL is one of the main ligands that activates the apoptosis extrinsic pathway when binding with Fas (its receptor), generating a death signal that activates caspase-8, which activates caspase-3 (the main initiator caspase of the apoptosis extrinsic pathway) producing the apoptotic cellular damage [3–5]. In addition, FasL also activates necroptosis [14–18], which is another type of programmed cell death. In necroptosis, an active and well-regulated necrosis occurs. Necroptosis is morphologically and biochemically different of apoptosis. Necroptosis is independent of caspases and is regulated by receptor-interacting protein (RIP) kinases. Necroptosis is activated by FasL and TRAIL when a compromised caspase-8 exists. Then, RIP1 and RIP3 are activated and form necrosomes with mixed-lineage kinase domain-like protein (MLKL) that translocates from cytosol to mitochondria leading to necroptotic cell changes. Active caspase-8 inhibits necroptosis via cleavage of RIP1 and RIP3. Inhibition of caspase leads to the formation of complex of RIP1 and RIP3 complex. Biochemical changes that appear during necroptosis include calcium overload, reactive oxygen species generation and adenosine triphosphate (ATP) depletion. Necroptosis is characterized by loss of plasma membrane integrity and organelle swelling, and finally cellular collapse appears. Therefore, we think that our findings on higher serum sFasL in non-survivors in respect to survivor patients could mean that non-surviving patients showed higher activation of apoptosis extrinsic pathway and of necroptosis that lead to higher cell death.