Redox-Active Quinones and Ascorbate: An Innovative Cancer Therapy That Exploits the Vulnerability of Cancer Cells to Oxidative Stress

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dc.contributor.authorVerrax, Julien
dc.contributor.authorBeck, Raphael
dc.contributor.authorDejeans, Nicolas
dc.contributor.authorGlorieux, Christophe
dc.contributor.authorSid, Brice
dc.contributor.authorPedrosa, Rozangela C.
dc.contributor.authorBenites, Julio
dc.contributor.authorVasquez, David
dc.contributor.authorValderrama, Jaime A.
dc.contributor.authorBuc Calderon, Pedro
dc.date.accessioned2024-01-10T12:08:03Z
dc.date.available2024-01-10T12:08:03Z
dc.date.issued2011
dc.description.abstractCancer cells are particularly vulnerable to treatments impairing redox homeostasis. Reactive oxygen species (ROS) can indeed play an important role in the initiation and progression of cancer, and advanced stage tumors frequently exhibit high basal levels of ROS that stimulate cell proliferation and promote genetic instability. In addition, an inverse correlation between histological grade and antioxidant enzyme activities is frequently observed in human tumors, further supporting the existence of a redox dysregulation in cancer cells. This biochemical property can be exploited by using redox-modulating compounds, which represent an interesting approach to induce cancer cell death. Thus, we have developed a new strategy based on the use of pharmacologic concentrations of ascorbate and redox-active quinones. Ascorbate-driven quinone redox cycling leads to ROS formation and provokes an oxidative stress that preferentially kills cancer cells and spares healthy tissues. Cancer cell death occurs through necrosis and the underlying mechanism implies an energetic impairment (ATP depletion) that is likely due to glycolysis inhibition. Additional mechanisms that participate to cell death include calcium equilibrium impairment and oxidative cleavage of protein chaperone Hsp90. Given the low systemic toxicity of ascorbate and the impairment of crucial survival pathways when associated with redox-active quinones, these combinations could represent an original approach that could be combined to standard cancer therapy.
dc.fechaingreso.objetodigital2024-05-17
dc.format.extent9 páginas
dc.fuente.origenWOS
dc.identifier.doi10.2174/187152011795255902
dc.identifier.eissn1875-5992
dc.identifier.issn1871-5206
dc.identifier.pubmedidMEDLINE:21395522
dc.identifier.urihttps://doi.org/10.2174/187152011795255902
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76352
dc.identifier.wosidWOS:000290613000007
dc.information.autorucQuímica;Valderrama J ;S/I;98772
dc.information.autorucQuímica;Vasquez D ;S/I;117510
dc.issue.numero2
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final221
dc.pagina.inicio213
dc.publisherBENTHAM SCIENCE PUBL LTD
dc.revistaANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
dc.rightsacceso restringido
dc.subjectAscorbate
dc.subjectcancer
dc.subjectquinone
dc.subjectredox cycling
dc.subjectoxidative stress
dc.subjectGLUTATHIONE-S-TRANSFERASE
dc.subjectCOMBINED VITAMIN-C
dc.subjectANTIOXIDANT ENZYMES
dc.subjectPEROXIREDOXIN-I
dc.subjectPHASE-I
dc.subjectMITOCHONDRIAL RESPIRATION
dc.subjectDIFFERENTIAL EXPRESSION
dc.subjectTHIOREDOXIN REDUCTASE
dc.subjectSUPEROXIDE-DISMUTASE
dc.subjectSOLUBLE ANTIOXIDANTS
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleRedox-Active Quinones and Ascorbate: An Innovative Cancer Therapy That Exploits the Vulnerability of Cancer Cells to Oxidative Stress
dc.typeartículo
dc.volumen11
sipa.codpersvinculados98772
sipa.codpersvinculados117510
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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