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Cellular and Molecular Life Sciences :... Sep 2022Oncosis (from Greek ónkos, meaning "swelling") is a non-apoptotic cell death process related to energy depletion. In contrast to apoptosis, which is the main form of...
Oncosis (from Greek ónkos, meaning "swelling") is a non-apoptotic cell death process related to energy depletion. In contrast to apoptosis, which is the main form of cell death induced by anticancer drugs, oncosis has been relatively less explored but holds potential to overcome drug resistance phenomena. In this study, we report a novel rationally designed mitochondria-targeted iridium(III) complex (OncoIr3) with advantageous properties as a bioimaging agent. OncoIr3 exhibited potent anticancer activity in vitro against cancer cells and displayed low toxicity to normal dividing cells. Flow cytometry and fluorescence-based assays confirmed an apoptosis-independent mechanism involving energy depletion, mitochondrial dysfunction and cellular swelling that matched with the oncotic process. Furthermore, a Caenorhabditis elegans tumoral model was developed to test this compound in vivo, which allowed us to prove a strong oncosis-derived antitumor activity in animals (with a 41% reduction of tumor area). Indeed, OncoIr3 was non-toxic to the nematodes and extended their mean lifespan by 18%. Altogether, these findings might shed new light on the development of anticancer metallodrugs with non-conventional modes of action such as oncosis, which could be of particular interest for the treatment of apoptosis-resistant cancers.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Death; Cell Line, Tumor; Iridium; Necrosis; Neoplasms
PubMed: 36066676
DOI: 10.1007/s00018-022-04526-5 -
Seminars in Cancer Biology Oct 2017Artemisia annua L. is used throughout Asia and Africa as tea and press juice to treat malaria and related symptomes (fever, chills). Its active ingredient, artemisinin... (Review)
Review
Artemisia annua L. is used throughout Asia and Africa as tea and press juice to treat malaria and related symptomes (fever, chills). Its active ingredient, artemisinin (ARS), has been developed as antimalarial drug and is used worldwide. Interestingly, the bioactivity is not restricted to malaria treatment. We and others found that ARS-type drugs also reveal anticancer in vitro and in vivo. In this review, we give a systematic overview of the literature published over the past two decades until the end of 2016. Like other natural products, ARS acts in a multi-specific manner against tumors. The cellular response of ARS and its derivatives (dihydroartemisinin, artesunate, artemether, arteether) towards cancer cells include oxidative stress response by reactive oxygen species and nitric oxide, DNA damage and repair (base excision repair, homologous recombination, non-homologous end-joining), various cell death modes (apoptosis, autophagy, ferroptosis, necrosis, necroptosis, oncosis), inhibition of angiogenesis and tumor-related signal transduction pathways (e.g. Wnt/β-catenin pathway, AMPK pathway, metastatic pathways, and others) and signal transducers (NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc). ARS-type drugs are at the stairways to the clinics. Several published case reports and pilot phase I/II trials indicate clinical anticancer activity of these compounds. Because of unexpected cases of hepatotoxicity, combinations of ARS-type drugs with complementary and alternative medicines are not recommended, until controlled clinical trials will prove the safety of non-approved combination treatments.
Topics: Artemisia annua; Artemisinins; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Proteins; Neoplasms; Oxidative Stress
PubMed: 28254675
DOI: 10.1016/j.semcancer.2017.02.009 -
Molecular and Cellular Biochemistry Feb 2005The rational design of therapeutic interventions for protection of ischemic myocardium from ultimate death requires an understanding of the mechanistic basis of... (Review)
Review
The rational design of therapeutic interventions for protection of ischemic myocardium from ultimate death requires an understanding of the mechanistic basis of cardiomyocyte (CM) cell death, its timing and the tools for its quantification. Until recently, CM cell death following ischemia and/or reperfusion was considered to involve necrosis or 'accidental cell death' from very early on. Collective evidence over the past decade indicates that early CM cell death after myocardial ischemia and post-ischemic reperfusion involves apoptosis with cell shrinkage and drop-out, and/or oncosis with cell swelling followed by necrosis. This paradigm shift suggests that different approaches for cardioprotection are required. Oncologists, pathologists, anatomists and basic scientists who have studied apoptosis over the last three decades separated physiological apoptosis from inappropriate apoptosis in pathological states. Until recently, cardiologists resisted the concepts of CM apoptosis and regeneration. Cumulative evidence indicating that apoptosis in the heart may occur in different cell types, spread from one cell type to another, and occur in bursts, may have profound implications for therapies aimed at protection of ischemic myocardium by targeting CM apoptosis in acute coronary syndromes. This review focuses on a critique of the methods used for the assessment of CM apoptosis and the implications of CM apoptosis in acute coronary syndromes.
Topics: Animals; Annexin A5; Apoptosis; Arteriosclerosis; Biomarkers; DNA; DNA Fragmentation; Humans; In Situ Nick-End Labeling; Ischemia; Microscopy, Electron; Microscopy, Fluorescence; Models, Biological; Myocardial Ischemia; Myocytes, Cardiac; Necrosis; Reperfusion Injury; Signal Transduction
PubMed: 15792367
DOI: 10.1007/s11010-005-4507-9 -
Biochimica Et Biophysica Acta Oct 1996Understanding the processes and events that occur when a cell undergoes a prelethal injury or that lead the cell to death following a lethal injury has been the aim of... (Review)
Review
Understanding the processes and events that occur when a cell undergoes a prelethal injury or that lead the cell to death following a lethal injury has been the aim of our research for a number of years. Throughout this period much has been learned, recently at rapid rates, not only by us but by many other investigators as well. Based on the data gathered, we proposed a working hypothesis over a decade ago and have since continually updated it as new experimentation is performed. Our laboratory has focused particularly on the role of cytoplasmic ionized calcium ([Ca2+]i) and the effects of its deregulation on prelethal events, including oncosis and apoptosis, and lethal events (necrosis) following cell death. [Ca2+]i appears to be a major link and signalling event. Understanding the mechanisms involved by using a variety of in vivo and in vitro models, coupled with state-of-the-art methodologies, should now allow us to prevent cell death by killing cells when necessary through gene therapy and cancer chemotherapy.
Topics: Animals; Calcium; Cell Death; Cytoplasm
PubMed: 8898851
DOI: 10.1016/0167-4889(96)00086-9 -
The Annals of Thoracic Surgery Jan 2004
Topics: Apoptosis; Humans; Ischemia; Myocytes, Cardiac; Necrosis
PubMed: 14726113
DOI: 10.1016/s0003-4975(02)05014-2 -
Pancreas Oct 1998Alterations in pancreatic cell function and morphology are characteristics of pancreatic compromise in various pathophysiological conditions. The present review focuses... (Review)
Review
Alterations in pancreatic cell function and morphology are characteristics of pancreatic compromise in various pathophysiological conditions. The present review focuses on potential patterns of pancreatic cell death, apoptosis, and/or oncosis, after different experimental challenges, to understand their potential significance in the pathogenesis of pancreatic injury. Apoptosis is not only present during maintenance of pancreatic homeostasis but can also be initiated by extrinsic and intrinsic factors. Pancreatic cell oncosis is another pattern of cell death, occurring in pancreatic injury. The proportion of apoptosis and oncosis may depend on the severity of pancreatic cell compromise, the properties of the challenge, animal strain, and time course. The role of various inflammatory mediators and adhesion molecules, the use of transgenic animals, and the significance of apoptosis and oncosis in acute and chronic pancreatic injury are discussed. Molecular biology of pancreatic cell death provides valuable information to simplify the understanding of mechanisms in clinical pancreatic diseases and may also introduce potential modes of pharmacological management.
Topics: Animals; Apoptosis; Cell Death; Humans; Mice; Mice, Transgenic; Pancreas; Pancreatic Ducts
PubMed: 9788543
DOI: 10.1097/00006676-199810000-00010 -
Advanced Science (Weinheim,... Sep 2021Oncosis, depending on DNA damage and mitochondrial swelling, is an important approach for treating cancer and other diseases. However, little is known about the behavior...
Oncosis, depending on DNA damage and mitochondrial swelling, is an important approach for treating cancer and other diseases. However, little is known about the behavior of mitochondria during oncosis, due to the lack of probes for in situ visual illumination of the mitochondrial membrane and mtDNA. Herein, a mitochondrial lipid and mtDNA dual-labeled probe, MitoMN, and a continuous add-on assay, are designed to image the dynamic process of mitochondria in conditions that are unobservable with current mitochondrial probes. Meanwhile, the MitoMN can induce oncosis in a light-activated manner, which results in the enlargement of mitochondria and the death of cancer cells. Using structured illumination microscopy (SIM), MitoMN-stained mitochondria with a dual-color response reveals, for the first time, how swelled mitochondria interacts and fuses with each other for a nonlinear enlargement to accelerate oncosis into an irreversible stage. With this sign of irreversible oncosis revealed by MitoMN, oncosis can be segregated into three stages, including before oncosis, initial oncosis, and accelerated oncosis.
Topics: Cell Death; Cells, Cultured; DNA, Mitochondrial; Equipment Design; Light; Microscopy; Mitochondria; Mitochondrial Membranes
PubMed: 34197052
DOI: 10.1002/advs.202004566 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Oct 2002
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Molecular Aspects of Medicine Jun 2009Oxysterols resulting from spontaneous or enzymatic oxidation of cholesterol are present in numerous foodstuffs and have been identified at increased levels in the plasma... (Review)
Review
Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis.
Oxysterols resulting from spontaneous or enzymatic oxidation of cholesterol are present in numerous foodstuffs and have been identified at increased levels in the plasma and the vascular walls of patients with cardiovascular diseases, especially in atherosclerotic lesions. Consequently, their role in lipid disorders is widely suspected, but they may also contribute to the development of important degenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, osteoporosis, age-related macular degeneration, and cataract. Since these pathologies can be associated with the presence of apoptotic cells, oxidative and inflammatory processes, and lipid disorders, the ability of oxysterols to trigger cell death, activate oxidation and inflammation, and modulate lipid homeostasis is being extensively studied. There are several important considerations regarding the physiological/pathophysiological functions and activities of the different oxysterols. It is therefore important to determine their biological activities and identify their signaling pathways, when they are used either in isolation or as mixtures. In these conditions, oxysterols may have cytotoxic, oxidative, and/or inflammatory effects, or no effects whatsoever. Moreover, with cytotoxic oxysterols, a substantial accumulation of polar lipids in cytoplasmic multilamellar structures was observed, demonstrating that cytotoxic oxysterols were phospholipidosis inducers. This basic knowledge on oxysterols contributes to a better understanding of the associated pathologies, so that new treatments and drugs can be designed.
Topics: Apoptosis; Atherosclerosis; Humans; Hydroxycholesterols; Inflammation; Ketocholesterols; Lipidoses; Macular Degeneration; Neoplasms; Oxidative Stress; Phospholipids
PubMed: 19248805
DOI: 10.1016/j.mam.2009.02.006 -
Journal of Immunological Methods Jul 2002Apoptosis and primary necrosis are the two modes of cell death induced by a lethal injury. The majority of structural and biochemical events occurring during cell death... (Review)
Review
Apoptosis and primary necrosis are the two modes of cell death induced by a lethal injury. The majority of structural and biochemical events occurring during cell death can be analysed by flow cytometry. The 7-aminoactinomycin D (7-AAD) assay can be used to detect the loss of membrane integrity during apoptosis of murine thymocytes and human peripheral lymphocytes. We describe here new applications of the 7-AAD assay. It can be applied to a variety of cell lines of different origins, including adherent cell lines, and it allows the co-detection of lipidic antigens such as phosphatidylserine (PS) residues, and biochemical processes linked to apoptosis, such as the loss of mitochondrial transmembrane potential, cardiolipin peroxidation, the expression of the 7A6 mitochondrial antigen and DNA fragmentation. Thus, this assay is a noninvasive method particularly adapted to the analysis of biochemical events associated with cell death. Finally, we show that this assay is not specific for apoptosis since it detects oncosis, the early stage of primary necrosis.
Topics: Apoptosis; Caspases; DNA Fragmentation; Dactinomycin; Flow Cytometry; Humans; Jurkat Cells; Mitochondria; T-Lymphocytes
PubMed: 12072180
DOI: 10.1016/s0022-1759(02)00072-8