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Authordc.contributor.authorJara Sandoval, José Antonio 
Authordc.contributor.authorRojas Rivera, Diego 
Authordc.contributor.authorCastro Castillo, Vicente 
Authordc.contributor.authorFuentes Retamal, Sebastián 
Authordc.contributor.authorSandoval Acuña, Cristian 
Authordc.contributor.authorParra, Eduardo 
Authordc.contributor.authorPavani, Mario 
Authordc.contributor.authorMaya Arango, Juan Diego 
Authordc.contributor.authorFerreira Parker, Jorge 
Authordc.contributor.authorCatalán Díaz, Mabel 
Cita de ítemdc.identifier.citationToxicology in Vitro 65: (2020): 104814es_ES
Abstractdc.description.abstractIntroduction: Colorectal cancer (CRC) is a critical health issue worldwide. The high rate of liver and lung metastasis associated with CRC creates a significant barrier to effective and efficient therapy. Tumour cells, including CRC cells, have metabolic alterations, such as high levels of glycolytic activity, increased cell proliferation and invasiveness, and chemo- and radio-resistance. However, the abnormally elevated mitochondrial transmembrane potential of these cells also provides an opportunity to develop drugs that selectively target the mitochondrial functions of tumour cells. Methods: In this work, we used a new batch of benzoic acid esters with cytotoxic activities attached to the triphenylphosphonium group as a vehicle to target tumour mitochondria and improve their activity. We evaluated the cytotoxicity, selectivity, and mechanism of action of these derivatives, including the effects on energy stress-induced apoptosis and metabolic behaviour in the human CRC cell lines HCT-15 and COLO-205. Results: The benzoic acid derivatives selectively targeted the tumour cells with high potency and efficacy. The derivatives induced the uncoupling of the oxidative phosphorylation system, decreased the transmembrane potential, and reduced ATP levels while increasing AMPK activation, thereby triggering tumour cell apoptosis in both tumour cell lines tested. Conclusion: The benzoic acid derivatives studied here are promising candidates for assessing in vivo models of CRC, despite the diverse metabolic characteristics of these tumour cells.es_ES
Patrocinadordc.description.sponsorshipConsejo Nacional de Ciencia y Tecnologia (CONACyT) Comisión Nacional de Investigación Cientifica y Tecnológica (CONICYT) FONDECYT 11160281 FONDECYT 1180296 FONDECYT 1130189 Academy Insertion Grant 791220004 Vicerrectoría de Investigación y Desarrollo, Universidad de Chile (Enlace) ENL022/16 Comisión Nacional de Investigación Cientifica y Tecnológica (CONICYT) FONDECYT 11160281 Comisión Nacional de Investigación Cientifica y Tecnológica (CONICYT) CONICYT FONDECYT 1180296 1130189 Universidad de Chile (Enlace) ENL022/16es_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
Link to Licensedc.rights.uri*
Sourcedc.sourceToxicology in Vitroes_ES
Keywordsdc.subjectTargeting mitochondriaes_ES
Keywordsdc.subjectBenzoic acid derivativeses_ES
Keywordsdc.subjectUncoupling agentses_ES
Keywordsdc.subjectMetabolism stresses_ES
Keywordsdc.subjectTriphenylphosphonium moietyes_ES
Keywordsdc.subjectColorectal canceres_ES
Keywordsdc.subjectAntitumour-mitochondrial agentses_ES
Títulodc.titleNovel benzoate-lipophilic cations selectively induce cell death in human colorectal cancer cell lineses_ES
Document typedc.typeArtículo de revistaes_ES
Indexationuchile.indexArtículo de publicación ISIes_ES

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Attribution-NonCommercial-NoDerivs 3.0 Chile
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile