Publicación:
Evaluación de la eficacia terapéutica de sulforafano y docetaxel sobre un modelo in vitro de cáncer de próstata

dc.contributor.advisorEspitia Pérez, Pedro Juanspa
dc.contributor.authorPeñata Taborda, Ana Marcela
dc.date.accessioned2023-01-28T01:59:12Z
dc.date.available2023-01-28T01:59:12Z
dc.date.issued2023-01-27
dc.description.abstractEl cáncer de próstata (CP) es la quinta causa de muerte a nivel mundial y la segunda neoplasia maligna mayormente diagnosticada en hombres, siendo la principal causa de muerte en la población masculina colombiana. Las células cancerosas de próstata muestran una actividad metabólica y redox anormal, y la evidencia emergente indica que el comportamiento de este tipo de cáncer se ha relacionado con características tumorales agresivas como la quimiorresistencia, invasividad y potencial metastásico, entre otras. Además, los medicamentos utilizados en oncología clínica tienen índices terapéuticos estrechos con toxicidad adversa, que a menudo implica daño oxidativo en los tejidos normales. El Docetaxel (DCT) es un fármaco antineoplásico, utilizado para el tratamiento de CP, su citotoxicidad y emergente resistencia han limitado su eficacia. Las terapias de combinación tienen el propósito de sensibilizar los tumores y proteger tejidos no afectados lo aumenta el índice terapéutico. El Sulforafano (SFN), es un fitoquímico de amplio interés clínico, debido a sus propiedades anticancerígenas y efectos promisorios en terapias de combinación. En consecuencia, la presente investigación tuvo como objetivo evaluar la eficacia terapeutica de SFN y DCT sobre un modelo in vitro de CP de diferente sensibilidad a quimioterapia como estrategia antitumoral. En esta investigación de tipo experimental, se usaron líneas celulares de CP con diferentes niveles de tumorigenicidad y quimioresistencia, así como la contraparte no tumoral, de modo que ofrecieran diferentes características redox y metabólicas.spa
dc.description.abstractProstate cancer (PC) is the fifth leading cause of death worldwide and the second most diagnosed malignancy in men, being the leading cause of death in the Colombian male population. Prostate cancer cells show abnormal metabolic and redox activity, and emerging evidence indicates that the behavior of this type of cancer has been related to aggressive tumor characteristics such as chemoresistance, invasiveness, and metastatic potential, among others. In addition, drugs used in clinical oncology have narrow therapeutic indexes with adverse toxicity, often involving oxidative damage to normal tissues. Docetaxel (DCT) is an antineoplastic drug used to treat PC; its cytotoxicity and emerging resistance have limited its efficacy. Combination therapies are intended to sensitize tumors and protect unaffected tissues, which increases the therapeutic index. Sulforaphane (SFN) is a phytochemical of broad clinical interest due to its anticancer properties and promising effects in combination therapies. Consequently, the present research aimed to evaluate the therapeutic efficacy of SFN and DCT on an in vitro model of PC with different sensitivity to chemotherapy as an antitumor strategy. In this experimental-type investigation, PC cell lines with different levels of tumorigenicity and chemoresistance, as well as the non-tumorigenic counterpart, were used to offer different redox and metabolic characteristics. eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Biotecnologíaspa
dc.description.modalityTrabajos de Investigación y/o Extensiónspa
dc.description.tableofcontentsLISTA DE FIGURAS ................................................................ 7spa
dc.description.tableofcontentsLISTA DE TABLAS........................................................................... 8spa
dc.description.tableofcontentsLISTA DE ANEXOS .............................................................................. 8spa
dc.description.tableofcontentsRESUMEN................................................................................ 9spa
dc.description.tableofcontentsABSTRACT ................................................................................ 11spa
dc.description.tableofcontentsINTRODUCCIÓN................................................................... 13spa
dc.description.tableofcontentsMARCO TEÓRICO Y ANTECEDENTES ............................................. 17spa
dc.description.tableofcontentsEtiología y patología del cáncer de próstata ...................................17spa
dc.description.tableofcontentsLa quimioterapia del cáncer de próstata .......................................19spa
dc.description.tableofcontentsEstrés Oxidativo y el cáncer de próstata .................................20spa
dc.description.tableofcontentsMetabolismo del cáncer de próstata...........................................22spa
dc.description.tableofcontentsFitoquímicos en el tratamiento del cáncer de próstata: Sulforafano..............25spa
dc.description.tableofcontentsOBJETIVOS......................................................................................... 27spa
dc.description.tableofcontentsObjetivo .......................................................................................27spa
dc.description.tableofcontentsObjetivos específicos.............................................................27spa
dc.description.tableofcontentsMATERIALES Y MÉTODOS...................................................... 28spa
dc.description.tableofcontentsÁrea y tipo de estudio ..............................................................28spa
dc.description.tableofcontentsCultivos celulares...............................................................28spa
dc.description.tableofcontentsEnsayo de viabilidad por Cristal violeta ..........................29spa
dc.description.tableofcontentsEnsayo de MTT [bromuro de 3- (4,5-dimetiltiazol-2-il) -2,5-difeniltetrazolio)] .............30spa
dc.description.tableofcontentsDetección y caracterización de la apoptosis .........................................31spa
dc.description.tableofcontentsEnsayo de muerte celular por Anexina V ...................................31spa
dc.description.tableofcontentsActividad caspasas 3, 8 y 9.............................................................31spa
dc.description.tableofcontentsEvaluación de los efectos combinados SFN y DCT mediante análisis de isobologramas ............32spa
dc.description.tableofcontentsCaracterización de los tratamientos combinados SFN y DCT sobre el estado redox y metabólico.....................................................................32spa
dc.description.tableofcontentsConsumo de glucosa y fermentación láctica......................................32spa
dc.description.tableofcontentsCaracterización redox .......................................................34spa
dc.description.tableofcontentsDeterminación de ROS intracelular.....................................34spa
dc.description.tableofcontentsMasa mitocondrial relativa ...........................................34spa
dc.description.tableofcontentsDeterminación de GSH, GSSG y la relación GSH/GSSG................35spa
dc.description.tableofcontentsNiveles de expresión (ARNm) de genes regulados por Nrf2, y HIF-1.............................36spa
dc.description.tableofcontentsAnálisis estadístico ..............................................................36spa
dc.description.tableofcontentsRESULTADOS ..................................................................... 37spa
dc.description.tableofcontentsDISCUSIÓN............................................................................ 51spa
dc.description.tableofcontentsCONCLUSIONES......................................................................... 59spa
dc.description.tableofcontentsREFERENCIAS BIBLIOGRAFICAS ........................................................ 60spa
dc.description.tableofcontentsANEXOS........................................................................................ 70spa
dc.format.mimetypeapplication/pdfspa
dc.identifier.urihttps://repositorio.unicordoba.edu.co/handle/ucordoba/6959
dc.language.isospaspa
dc.publisherUniversidad de Córdobaspa
dc.publisher.facultyFacultad de Ciencias Básicasspa
dc.publisher.placeMontería, Córdoba, Colombiaspa
dc.publisher.programQuímicaspa
dc.rightsCopyright Universidad de Córdoba, 2023spa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.creativecommonsAtribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)spa
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/spa
dc.subject.keywordsChemoresistanceeng
dc.subject.keywordsCombination therapyeng
dc.subject.keywordsSulforaphaneeng
dc.subject.keywordsGlycolysiseng
dc.subject.keywordsRedox metabolismeng
dc.subject.proposalQuimioresistenciaspa
dc.subject.proposalSulforafanospa
dc.subject.proposalTerapia de combinaciónspa
dc.subject.proposalGlucolisisspa
dc.subject.proposalMetabolismo redoxspa
dc.titleEvaluación de la eficacia terapéutica de sulforafano y docetaxel sobre un modelo in vitro de cáncer de próstataspa
dc.typeTrabajo de grado - Maestríaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdccspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/masterThesisspa
dc.type.redcolhttps://purl.org/redcol/resource_type/TMspa
dc.type.versioninfo:eu-repo/semantics/submittedVersionspa
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