Pharmacological Modulation of Reactive Oxygen Species in Cancer Treatment
| Autor: | Judit Ribas, Jacint Boix, Paolo Mattiolo |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
p53
Cell death Programmed cell death Estrès oxidatiu Clinical Biochemistry Cell Antineoplastic Agents Experimental pharmacology PES (2-phenylethynesulfonamide) Biology medicine.disease_cause Mitochondrial Dynamics Medicaments antineoplàstics Farmacologia experimental Neoplasms Drug Discovery Antineoplastic agents medicine pifithrin-mu Humans Buthionine Sulfoximine Central element Pharmacology chemistry.chemical_classification Sulfonamides Reactive oxygen species Autophagy Cell biology Gene Expression Regulation Neoplastic Oxidative Stress anticancer drugs medicine.anatomical_structure chemistry Biochemistry Proteotoxicity Apoptosis Mort cel·lular Oxidative stress Molecular Medicine Tumor Suppressor Protein p53 Reactive Oxygen Species |
| Zdroj: | Repositorio Abierto de la UdL Universitad de Lleida ResearcherID Recercat. Dipósit de la Recerca de Catalunya instname |
| Popis: | Aerobic metabolism of mammalian cells leads to the generation of reactive oxygen species (ROS). To cope with this toxicity, evolution provided cells with effective antioxidant systems like glutathione. Current anticancer therapies focus on the cancer dependence on oncogenes and non-oncogenes. Tumors trigger mechanisms to circumvent the oncogenic stress and to escape cell death. In this context we have studied 2-phenylethinesulfoxamine (PES), which disables the cell protective mechanisms to confront the proteotoxicity of damaged and unfolded proteins. Proteotoxic stress is increased in tumor cells, thus providing an explanation for the anticancer selectivity of PES. In addition, we have found that PES induces a severe oxidative stress and the activation of p53. The reduction of the cell content in glutathione by means of L-buthionine-sulfoximine (BSO) synergizes with PES. In conclusion, we have found that ROS constitutes a central element in a series of positive feed-back loops in the cell. ROS, p53, proteotoxicity, autophagy and mitochondrial dynamics are interconnected with the mechanisms leading to cell death, either apoptotic or necrotic. This network of interactions provides multiple targets for drug discovery and development in cancer. |
| Databáze: | OpenAIRE |
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