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dc.contributor.authorRibas i Fortuny, Judit
dc.contributor.authorMattiolo, Paolo
dc.contributor.authorBoix Torras, Jacint
dc.date.accessioned2015-03-20T17:37:54Z
dc.date.available2016-01-31T03:30:57Z
dc.date.issued2015-01-01
dc.identifier.issn1389-4501
dc.identifier.urihttp://hdl.handle.net/10459.1/48083
dc.description.abstractAerobic 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.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherBentham Science
dc.relation.isformatofVersió preprint del document publicat a: https://doi.org/10.2174/1389450115666141114153536
dc.relation.ispartofCurrent Drug Targets, 2015, vol. 16, num. 1, p. 31-37
dc.rights(c) Bentham Science, 2015
dc.subjectoxidative stress
dc.subjectanticancer drugs
dc.subjectp53
dc.subjectPES (2-phenylethynesulfonamide)
dc.subjectpifithrin-mu
dc.subject.classificationMort cel·lular
dc.subject.classificationEstrès oxidatiu
dc.subject.classificationFarmacologia experimental
dc.subject.classificationMedicaments antineoplàstics
dc.subject.otherCell death
dc.subject.otherOxidative stress
dc.subject.otherExperimental pharmacology
dc.subject.otherAntineoplastic agents
dc.titlePharmacological Modulation of Reactive Oxygen Species in Cancer Treatment
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2015-03-20T17:37:54Z
dc.identifier.idgrec021692
dc.type.versioninfo:eu-repo/semantics/submittedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.2174/1389450115666141114153536


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