Cancer and cell death

2019 ◽  
pp. 196-208
Author(s):  
Jessica Bullenkamp ◽  
Mahvash Tavassoli
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Tumour Growth ◽  
Cellular Proliferation ◽  
Control Cell ◽  
Treatment Strategies ◽  
Genetic Alterations ◽  
Constant Number ◽  
Normal Tissues ◽  
Multicellular Organisms

Programmed cell death is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. Regulated programmed cell death is one of the mechanisms by which multicellular organisms limit the growth and replication of cells. Cell death is essential to control cell growth and tissue homeostasis; it occurs in normal tissues to allow the removal of damaged cells or to maintain a constant number of cells in regenerating tissues and plays an important part in embryogenesis. In an average human adult 50–70 billion cells undergo programmed cell death every day. The abundance of literature suggests that defects in programmed cell death play a crucial role in carcinogenesis. The genetic alterations in the cancer cell not only lead to increased cellular proliferation, as discussed in other chapters of this book, but also lead to loss of programmed cell death, thus increasing tumour growth. Despite being part of the problem, cell death plays an important role in the treatment of cancer as it is an important target of many treatment strategies. Unquestionably, apoptosis is the best-characterized and the most evolutionary conserved form of programmed cell death. Recently, many studies have demonstrated the existence of several other forms of programmed cell death including autophagy, necroptosis, and pyroptosis. In this chapter we discuss several regulated forms of cell death; we outline what we know about their mechanisms and how we can exploit this knowledge to reactivate programmed cell death in tumour cells for the treatment of cancer.

scholarly journals TaMCA4, a Novel Wheat Metacaspase Gene Functions in Programmed Cell Death Induced by the Fungal Pathogen Puccinia striiformis f. sp. tritici

2012 ◽  
Vol 25 (6) ◽  
pp. 755-764 ◽  
Author(s):  
Xiaodong Wang ◽  
Xiaojie Wang ◽  
Hao Feng ◽  
Chunlei Tang ◽  
Pengfei Bai ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Fungal Pathogen ◽  
Puccinia Striiformis ◽  
Transcript Level ◽  
Structural Features ◽  
Virus Induced Gene Silencing ◽  
Wheat Leaves ◽  
Multicellular Organisms ◽  
Bax Gene

Programmed cell death (PCD) is a physiological process to remove redundant or harmful cells, for the development of multicellular organisms, or for restricting the spread of pathogens (hypersensitive response). Metacaspases are cysteine-dependent proteases which play an essential role in PCD. Triticum aestivum metacaspase 4 (TaMCA4) is a type II metacaspase gene cloned from ‘Suwon11’ wheat, with typical structural features such as peptidase C14 caspase domain and a long linker sequence between the two subunits. Transient expression of TaMCA4 in tobacco leaves failed to induce PCD directly but enhanced cell death triggered by a mouse Bax gene or a candidate effector gene from Puccinia striiformis f. sp. tritici. Enhancement of PCD was also observed in wheat leaves co-bombarded with TaMCA4. When challenged with the avirulent race of P. striiformis f. sp. tritici, the expression level of TaMCA4 in wheat leaves was sharply upregulated, whereas the transcript level was not significantly induced by the virulent race. Moreover, knocking down TaMCA4 expression by virus-induced gene silencing enhanced the susceptibility of Suwon11 to the avirulent race of P. striiformis f. sp. tritici and reduced the necrotic area at infection sites.

Cancer Immunotherapy-Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

2021 ◽  
Vol 16 ◽  
Author(s):  
Jing Bai ◽  
Ping Liang ◽  
Qian Li ◽  
Rui Feng ◽  
Jiang Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Locoregional Therapy ◽  
Incidence And Mortality

: Hepatocellular Carcinoma (HCC) is one of the most common malignancies, the incidence and mortality of which are increasing worldwide. Cancer immunotherapy has revolutionized cancer treatment in recent years. In particular, Immune Checkpoint Inhibitors (ICIs) as new therapeutic tools have demonstrated encouraging antitumor activity and manageable tolerability in HCC. Immunologic checkpoint blockade with antibodies targeting Programmed cell Death-1 (PD-1), Programmed cell Death Ligand-1 (PD-L1), and Cytotoxic T Lymphocyte-Associated protein-4 (CTLA-4) strengthens tumor immunity by restoring exhausted T cells. Although the efficacy of combination treatment strategies using ICIs combined with other ICIs, molecular targeted agents, systemic therapy, or locoregional therapy has been well documented in numerous preclinical and clinical studies on several types of cancers, most HCC patients do not benefit from ICI treatment. This review highlights recent developments and potential opportunities related to ICIs and their combination in the management of HCC. The present article also includes recent patent review coverage on this topic.

scholarly journals T-2 mycotoxin induced apoptosis in broiler’s liver tissue

2018 ◽  
Vol 27 (1) ◽  
pp. 9-16
Author(s):  
Piret Hussar ◽  
Tõnu Järveots ◽  
Lazo Pendovski ◽  
Katerina Blagoevska ◽  
Trpe Ristoski ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Liver Tissue ◽  
Immunohistochemical Staining ◽  
Mammalian Cells ◽  
Gallus Domesticus ◽  
Gallus Gallus Domesticus ◽  
Histopathological Changes ◽  
Induced Apoptosis ◽  
Multicellular Organisms

Apoptosis is a process of programmed cell death that occurs in multicellular organisms. As T-2 toxin is known to induce apoptosis in mammalian cells, the aim of the present experiment was to study the toxic effect of T-2 on chicken liver tissue using apoptosis-related antibodies p21 and p53 which are involved in the p53/p21-mediated apoptotic signalling pathway. The experiment was conducted on fourteen 40-day-old broilers (Gallus gallus domesticus) who were divided into control and T-2 toxin groups. For the T-2 toxin group, T-2 toxin (Sigma, Germany) was dissolved in water and given per os for three consecutive days. The material of the liver was taken 24 hours after the last application. The specimens were fixed with 10% formalin and embedded into paraffin; slices 5 μm in thickness were cut followed by immunohistochemical staining with polyclonal primary antibodies p21 and p53 (Abcam, UK) according to the manufacturer’s guidelines (IHC kit, Abcam, UK). Strong expression of p21 and p53 found in hepatocytes, endotheliocytes and around blood vessels together with large tissue destructions in T-2 toxin group birds’ liver indicates apoptosis and histopathological changes in liver tissue during T-2 mycotoxicosis.

scholarly journals A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in Escherichia coli

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Liselot Dewachter ◽  
Natalie Verstraeten ◽  
Daniel Monteyne ◽  
Cyrielle Ines Kint ◽  
Wim Versées ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cell Surface ◽  
Single Amino Acid ◽  
Altruistic Behavior ◽  
Membrane Blebbing ◽  
Cell Death Pathway ◽  
Higher Eukaryotes ◽  
Multicellular Organisms

ABSTRACT Programmed cell death (PCD) is an important hallmark of multicellular organisms. Cells self-destruct through a regulated series of events for the benefit of the organism as a whole. The existence of PCD in bacteria has long been controversial due to the widely held belief that only multicellular organisms would profit from this kind of altruistic behavior at the cellular level. However, over the past decade, compelling experimental evidence has established the existence of such pathways in bacteria. Here, we report that expression of a mutant isoform of the essential GTPase ObgE causes rapid loss of viability in Escherichia coli. The physiological changes that occur upon expression of this mutant protein—including loss of membrane potential, chromosome condensation and fragmentation, exposure of phosphatidylserine on the cell surface, and membrane blebbing—point to a PCD mechanism. Importantly, key regulators and executioners of known bacterial PCD pathways were shown not to influence this cell death program. Collectively, our results suggest that the cell death pathway described in this work constitutes a new mode of bacterial PCD. IMPORTANCE Programmed cell death (PCD) is a well-known phenomenon in higher eukaryotes. In these organisms, PCD is essential for embryonic development—for example, the disappearance of the interdigital web—and also functions in tissue homeostasis and elimination of pathogen-invaded cells. The existence of PCD mechanisms in unicellular organisms like bacteria, on the other hand, has only recently begun to be recognized. We here demonstrate the existence of a bacterial PCD pathway that induces characteristics that are strikingly reminiscent of eukaryotic apoptosis, such as fragmentation of DNA, exposure of phosphatidylserine on the cell surface, and membrane blebbing. Our results can provide more insight into the mechanism and evolution of PCD pathways in higher eukaryotes. More importantly, especially in the light of the looming antibiotic crisis, they may point to a bacterial Achilles’ heel and can inspire innovative ways of combating bacterial infections, directed at the targeted activation of PCD pathways.

scholarly journals An Endopolygalacturonase from Sclerotinia sclerotiorum Induces Calcium-Mediated Signaling and Programmed Cell Death in Soybean Cells

2005 ◽  
Vol 18 (8) ◽  
pp. 849-855 ◽  
Author(s):  
Anna Zuppini ◽  
Lorella Navazio ◽  
Luca Sella ◽  
Carala Castiglioni ◽  
Francesco Favaron ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Sclerotinia Sclerotiorum ◽  
Phase 1 ◽  
Control Cell ◽  
Cell Contact ◽  
Cytochrome C Release ◽  
Soybean Seedlings ◽  
Polygalacturonase Inhibiting Protein

A basic endopolygalacturonase (PG) isoform, produced early by Sclerotinia sclerotiorum when infecting soybean seedlings, was used to examine the signaling role of the enzyme in aequorin-expressing soybean cells. A cytosolic Ca2+ elevation was induced, with a rapid increase (phase 1) and a very slow decrease (phase 2) of Ca2+ concentration, indicating the involvement of Ca2+ ions in PG signaling. Within 1 h of PG-cell contact a remarkable level of cell death was recorded, significantly higher than the control cell culture turnover. The observed morphological and biochemical changes were indicative of the activation of programmed cell death; in particular, cytochrome c release in the cytoplasm and activation of both caspase 9-like and caspase 3-like proteases were found. When a polygalacturonase-inhibiting protein (PGIP) and the PG were simultaneously applied to cells, both the Ca2+ increase and cell death were annulled. The possible roles of prolonged sustained cytosolic Ca2+ concentrations in inducing cell death and of the PG-PGIP interaction in preventing PG signaling are discussed.

scholarly journals Caspases in Cell Death, Inflammation, and Pyroptosis

2020 ◽  
Vol 38 (1) ◽  
pp. 567-595 ◽  
Author(s):  
Sannula Kesavardhana ◽  
R.K. Subbarao Malireddi ◽  
Thirumala-Devi Kanneganti
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Responses ◽  
Cross Talk ◽  
Cysteine Proteases ◽  
Proteolytic Processing ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
New Research ◽  
Multicellular Organisms

Caspases are a family of conserved cysteine proteases that play key roles in programmed cell death and inflammation. In multicellular organisms, caspases are activated via macromolecular signaling complexes that bring inactive procaspases together and promote their proximity-induced autoactivation and proteolytic processing. Activation of caspases ultimately results in programmed execution of cell death, and the nature of this cell death is determined by the specific caspases involved. Pioneering new research has unraveled distinct roles and cross talk of caspases in the regulation of programmed cell death, inflammation, and innate immune responses. In-depth understanding of these mechanisms is essential to foster the development of precise therapeutic targets to treat autoinflammatory disorders, infectious diseases, and cancer. This review focuses on mechanisms governing caspase activation and programmed cell death with special emphasis on the recent progress in caspase cross talk and caspase-driven gasdermin D–induced pyroptosis.

scholarly journals The Reaper-Binding Protein Scythe Modulates Apoptosis and Proliferation during Mammalian Development

2005 ◽  
Vol 25 (23) ◽  
pp. 10329-10337 ◽  
Author(s):  
Fabienne Desmots ◽  
Helen R. Russell ◽  
Youngsoo Lee ◽  
Kelli Boyd ◽  
Peter J. McKinnon
Keyword(s):  
Cell Death ◽  
Drosophila Melanogaster ◽  
Programmed Cell Death ◽  
Xenopus Laevis ◽  
Cellular Proliferation ◽  
Nuclear Protein ◽  
Normal Development ◽  
Mammalian Development ◽  
Developmental Defects ◽  
Cell Extracts

ABSTRACT Scythe (BAT3 [HLA-B-associated transcript 3]) is a nuclear protein that has been implicated in apoptosis, as it can modulate Reaper, a central apoptotic regulator in Drosophila melanogaster. While Scythe can markedly affect Reaper-dependent apoptosis in Xenopus laevis cell extracts, the function of Scythe in mammals is unknown. Here, we report that inactivation of Scythe in the mouse results in lethality associated with pronounced developmental defects in the lung, kidney, and brain. In all cases, these developmental defects were associated with dysregulation of apoptosis and cellular proliferation. Scythe − / − cells were also more resistant to apoptosis induced by menadione and thapsigargin. These data show that Scythe is critical for viability and normal development, probably via regulation of programmed cell death and cellular proliferation.

scholarly journals “Programmed Cell Death: A Process of Death for Survival” – How Far Terminology Pertinent for Cell Death in Unicellular Organisms

2018 ◽  
Vol 11 ◽  
pp. 117906601879025 ◽  
Author(s):  
Shiv Shanker Pandey ◽  
Samer Singh ◽  
Chandramani Pathak ◽  
Budhi Sagar Tiwari
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Normal Growth ◽  
Death Process ◽  
Target Cells ◽  
Dna Ladder ◽  
Cell Death Process ◽  
Unicellular Organisms ◽  
Multicellular Organisms ◽  
Dna Nicks

Programmed cell death (PCD) is genetically regulated phenomenon of selective elimination of target cells that are either under pathological conditions or unwanted for organism’s normal growth and development due to other reasons. The process although being genetically controlled is physiological in nature that renders some hallmarks like blebs in the cell membrane, lobe formation in nuclear membrane, DNA nicks resulting to DNA ladder of 200 bp, and downstream activation of caspases. Moreover, as the process refers to the death of “targeted cell”, the term is exclusively suitable for multicellular organisms. Number of reports advocate similar type of cell death process in unicellular organisms. As cell death in unicellular organisms is also reflected by the signature of PCD obtained in metazoans, such cell death has been grouped under the broad category of PCD. It is pertinent to mention that by definition a unicellular organism is made of a single cell wherein it carries out all of its life processes. Using the term “Programmed Cell Death” with a preset “survival strategy of the organism” for unicellular organisms looks misnomer. Therefore, this correspondence argues and requests recommendation committee on cell death to revisit for the nomenclature of the cell death process in the unicellular organisms.

scholarly journals Evaluation of SYK Gene as a Prognostic Biomarker and Suggested Aromatic Potential Phytochemicals to Halt the Colorectal Cancer

2021 ◽  
Author(s):  
Partha Biswas ◽  
Dipta Dey ◽  
Atikur Rahman ◽  
Md. Aminul Islam ◽  
Tasmina Ferdous Susmi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Docking ◽  
Drug Repositioning ◽  
Treatment Strategies ◽  
Interaction Network ◽  
Genetic Alterations ◽  
Gene Encoding ◽  
Protein Protein Interaction ◽  
Normal Tissues ◽  
Potential Biomarker

Background: Colorectal cancer is considered the third most fetal among all type of cancer. Spleen tyrosine kinase (SYK) is a non-receptor type tyrosine-protein that plays crucial role in signaling mediated via immune receptor. We adopted an onco-informatics analysis to evaluate the SYK expression and prognostic value of SYK in colorectal cancer, and identification of potential phytochemicals which may inhibit overexpression of SYK protein as well as minimized colorectal cancer. Materials & Methods: Differential expression of SYK gene was analyzed using the several transcriptomic databases including Oncomine, UALCAN, GENT2 and GEPIA2. The server, cBioPortal was used to analyze mutation and copy number alterations whereas GENT2, GEPIA, OncoLnc and PrognoScan were employed to examine the survival rate. A protein-protein interaction network of SYK and co-expressed genes of SYK was conducted via GeneMANIA. Considering SYK gene encoding protein as drug target, selected phytochemicals were assessed by molecular docking using PyRx 0.8 packages. YASARA molecular dynamics simulators were applied for the post validation of the molecular docking data. Results: We have observed significant overexpression of mRNA expression levels of SYK gene colorectal adenocarcinoma (COAD) samples compared with normal tissues. Significant methylation level and various genetic alterations are assembled in SYK gene which can lead to the development of colorectal cancer. As a result, lower level of SYK expression was related to the more chances of patients’ survival by which all the outcomes from the multiple bioinformatics platforms and web resources have demonstrated the significant evidences that the SYK kinsase can possess as a potential biomarker for the treatment of colorectal cancer. Here, aromatic phytochemicals namely, Kaempferol and Glabridin targeting SYK showed more stability compared to controls and may be useful for the treatment of colorectal cancer. Conclusion: Our study showed dysregulated expression of SYK in colorectal cancer and potentiality to act as a biomarker for the prognosis of CRC. Moreover, we have shown phytochemicals (Kaempferol and Glabridin) target SYK as potential treatment strategies and drug repositioning potentiality in colorectal cancer.

scholarly journals Disturbances in the Mechanism of Apoptosis as One of the Causes of the Development of Cancer Diseases

2020 ◽  
Vol 18 (4) ◽  
pp. 63-73
Author(s):  
Paweł Rusin ◽  
Karolina Jabłońska
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Death Receptor ◽  
The Body ◽  
Stress Factors ◽  
Cancerous Cell ◽  
Anticancer Treatment ◽  
Apoptotic Pathways ◽  
Apoptosis Regulation ◽  
Multicellular Organisms

Apoptosis is a genetically programmed process that affects all multicellular organisms. This mechanism of programmed cell death is designed to protect the body against uncontrolled proliferation of cells with impaired functions. Apoptosis can occur through two major pathways. The extrinsic, initiated by signals from the death receptor, and the intrinsic one, resulting from a change in the permeability of the external mitochondrial membrane due to stress factors promoting the initiation of programmed cell death. Apoptosis may be influenced by many factors that may lead to suppressing the initiation of apoptotic pathways, and the damaged cell will develop, divide, and over time transform into a cancerous cell. As a result, cancer cells will be resistant to the applied chemo- and radiotherapy. The mechanisms responsible for apoptosis regulation are impaired, what eliminates the effects of therapies aimed at initiating this type of cell death. New types of molecular therapies provide an opportunity to increase the effectiveness of anticancer treatment, aiming at deficient proteins and suppressing or eliminating their antiapoptotic effects.

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