Search results for "Cell Death"

Parthenolide and Its Soluble Analogues: Multitasking Compounds with Antitumor Properties

2022

Due to its chemical properties and multiple molecular effects on different tumor cell types, the sesquiterpene lactone parthenolide (PN) can be considered an effective drug with significant potential in cancer therapy. PN has been shown to induce either classic apoptosis or alternative caspase-independent forms of cell death in many tumor models. The therapeutical potential of PN has been increased by chemical design and synthesis of more soluble analogues including dimethylaminoparthenolide (DMAPT). This review focuses on the molecular mechanisms of both PN and analogues action in tumor models, highlighting their effects on gene expression, signal transduction and execution of different ty…

Deglycosylated bleomycin triggers apoptosis in laryngeal carcinoma cells in a caspase and reactive oxygen species independent manner

2008

Background:  Bleomycin-A2, a member of a family of glycopeptide antibiotics, has potent antitumor activity against a range of lymphomas, head and neck cancer and germ cell tumors. However, little is known about the biologic activity of the carbohydrate moiety in Bleomycin-A2-induced cytotoxicity. Methods:  We compared the capacity of Bleomycin-A2 and its deglycosylated form (deglycoBleomycin-A2) to induce cell death. Apoptosis was analyzed by cell nuclear staining with Hoechst 33342 dye and DNA fragmentation. The signal transduction pathway was measured through Western blotting and production of reactive oxygen species (ROS). Results:  When tested on HEp-2 laryngeal carcinoma cells, Bleomyc…

Interplays between nitric oxide and reactive oxygen species in cryptogein signalling

2014

The cellular messenger nitric oxide (NO) has many functions in plants. In this study, we investigated its interplays with Reactive Oxygen Species (ROS) in the defense responses triggered by the elicitin cryptogein produced by the oomycete Phytophthora cryptogea. The production of NO induced by cryptogein in tobacco cell suspensions was partly regulated through a ROS-dependent pathway involving the NADPH oxidase NtRBOHD. In turn, NO down-regulated the level of H2O2 derived from NtRBOHD activity. Both NO and ROS synthesis appeared to be under the control of two redundant isoforms of histone deacetylases of type 2 acting as negative regulators of cell death. Occurrence of an interplay between …

Mitochondrial oxidative stress and CD95 ligand: A dual mechanism for hepatocyte apoptosis in chronic alcoholism

2002

Apoptosis plays an important role in the progression of alcohol-induced liver disease to cirrhosis. Oxidative stress is an early event in the development of apoptosis. The major aim of this study was to study the conditions in which oxidative stress occurs in chronic alcoholism and its relationship with apoptosis of hepatocytes. We have found that oxidative stress is associated with chronic ethanol consumption in humans and in rats, in the former independently of the existence of alcohol-induced liver disease. Ethanol or acetaldehyde induces apoptosis in hepatocytes isolated from alcoholic rats, but not in those from control rats. Inhibition of aldehyde dehydrogenase, but not of cytochrome …

The Relationship between Alcohol–induced Apoptosis and Oxidative Stress in the Liver

2005

This chapter discusses the relationship of apoptosis and oxidative stress induced by alcohol in the liver. Oxidative stress is involved in the pathogenesis and progression of alcohol-induced liver disease. Chronic alcoholism always causes oxidative stress independently of the presence of liver disease. Two key mechanisms are responsible for it: (1) the mitochondrial respiratory chain and (2) cytochrome P450 2El activity. Increased production of reactive oxygen species at complexes I and III together with NADH overproduction would be the major cause for mitochondrial oxidative stress in chronic alcoholism. Reactive Oxygen Species (ROS) cause oxidative damage, which may lead to cell death by …

17β-Estradiol-dependent regulation of chaperone expression and telomerase activity in the marine sponge Geodia cydonium

1999

It is known that species belonging to the lowest metazoan phylum, the Porifera (sponges), do not develop tumors. Sponge cells share with tumor cells of higher animals at least one characteristic; they contain high levels of telomerase activity, suggesting that they possess a high proliferation capacity. This assumption, however, has not been substantiated experimentally. In addition, sponges show a specific bauplan, leading us to postulate that they undergo apoptosis to replace a given set of cells at a given time. In the present study, 17β-estradiol (βE2) was used as a defined agent to assess its effect on both the telomerase activity and the process of apoptosis in the marine sponge Geodi…

Oxidative stress in diabetic retinopathy

2020

Diabetic retinopathy (DR) is the leading cause of acquired blindness in working adults worldwide. Biochemical changes in DR contribute to both the microscopic structural and functional changes in the retina. All these alterations result in retinal damage that can be assessed by funduscopy, optical coherence tomography (OCT), and angioOCT. Reactive oxygen species (ROS) overproduction in the mitochondria is considered a causal link between elevated glucose and biochemical abnormalities in the pathophysiology of DR. Moreover, oxidative-induced pathways also seem to provide positive feedback to ROS production, resulting in a vicious cycle. ROS can directly damage lipids, proteins, and DNA, lead…

Diabetic Retinopathy and Oxidative Stress

2014

Abstract Diabetic retinopathy (DR) is the leading cause of acquired blindness in working age adults worldwide. Biochemical changes in DR contribute to both the microscopic structural and functional changes in the retina. All these alterations result in macroscopic retinal damage that can be assessed by funduscopy. The overproduction of reactive oxygen species (ROS) in the mitochondria is considered a causal link between elevated glucose and biochemical abnormalities in the pathophysiology of DR. Moreover, oxidatively induced pathways also seem to provide positive feedback to ROS production, resulting in a vicious cycle. ROS can directly damage lipids, proteins and DNA, leading to cell death…

Activation of Mitochondria-Driven Pathways by Artemisinin and Its Derivatives

2014

Mitochondria have recently emerged as promising agents for cancer therapy. Of particular interest and potential clinical relevance are agents that target these organelles, promoting cell death. There are literally thousands of compounds that act on mitochondria and destabilise them. Of these, naturally occurring compounds are particularly interesting, since they are often more ‘biocompatible’; besides, natural compounds can be lead drugs for the design of novel and more efficient anti-cancer agents. In this paper, we focus on the natural product artemisin and its semisynthetic derivatives, and document the molecular mechanism of their activity and their potential use as clinically relevant …

2021

Myoglobin (MB) is an oxygen-binding protein usually found in cardiac myocytes and skeletal muscle fibers. It may function as a temporary storage and transport protein for O2 but could also have scavenging capacity for reactive oxygen and nitrogen species. In addition, MB has recently been identified as a hallmark in luminal breast cancer and was shown to be robustly induced under hypoxia. Cellular responses to hypoxia are regulated by the transcription factor hypoxia-inducible factor (HIF). For exploring the function of MB in breast cancer, we employed the human cell line MDA-MB-468. Cells were grown in monolayer or as 3D multicellular spheroids, which mimic the in vivo avascular tumor arch…