Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica
The cytotoxic effect of different Colombian Piper plants was determined by the MTT assay in human cancer cell lines A549 (lung), PC-3 (prostate) and MDAMB-231 (breast). The most potent cytotoxic effect was found in the leaves ethanolic extract of P. eriopodon with IC50 values less than 25 μg/mL. Aft...
- Autores:
-
Muñoz Cendales, Diego Ricardo
- Tipo de recurso:
- Doctoral thesis
- Fecha de publicación:
- 2020
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/77848
- Acceso en línea:
- https://repositorio.unal.edu.co/handle/unal/77848
- Palabra clave:
- 540 - Química y ciencias afines
Cáncer
Apoptosis
Muerte independiente de caspasas
XIAP
Alquenilfenoles
Piper eriopodon
Cancer
Apoptosis
Caspase independent cell death
XIAP
Alkenylphenols
Piper eriopodon
- Rights
- openAccess
- License
- Atribución-NoComercial 4.0 Internacional
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| dc.title.spa.fl_str_mv |
Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica |
| title |
Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica |
| spellingShingle |
Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica 540 - Química y ciencias afines Cáncer Apoptosis Muerte independiente de caspasas XIAP Alquenilfenoles Piper eriopodon Cancer Apoptosis Caspase independent cell death XIAP Alkenylphenols Piper eriopodon |
| title_short |
Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica |
| title_full |
Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica |
| title_fullStr |
Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica |
| title_full_unstemmed |
Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica |
| title_sort |
Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica |
| dc.creator.fl_str_mv |
Muñoz Cendales, Diego Ricardo |
| dc.contributor.advisor.spa.fl_str_mv |
Cuca Suarez, Luis Enrique |
| dc.contributor.author.spa.fl_str_mv |
Muñoz Cendales, Diego Ricardo |
| dc.contributor.researchgroup.spa.fl_str_mv |
Química de Productos Naturales Vegetales Bioactivos |
| dc.subject.ddc.spa.fl_str_mv |
540 - Química y ciencias afines |
| topic |
540 - Química y ciencias afines Cáncer Apoptosis Muerte independiente de caspasas XIAP Alquenilfenoles Piper eriopodon Cancer Apoptosis Caspase independent cell death XIAP Alkenylphenols Piper eriopodon |
| dc.subject.proposal.spa.fl_str_mv |
Cáncer Apoptosis Muerte independiente de caspasas XIAP Alquenilfenoles Piper eriopodon |
| dc.subject.proposal.eng.fl_str_mv |
Cancer Apoptosis Caspase independent cell death XIAP Alkenylphenols Piper eriopodon |
| description |
The cytotoxic effect of different Colombian Piper plants was determined by the MTT assay in human cancer cell lines A549 (lung), PC-3 (prostate) and MDAMB-231 (breast). The most potent cytotoxic effect was found in the leaves ethanolic extract of P. eriopodon with IC50 values less than 25 μg/mL. After different chromatographic techniques, nine alkenylphenols (1 - 9) were isolated from the ethanolic extract of leaves from P. eriopodon and their molecular structures were identified by the analysis of the spectroscopic data (IR; NMR 1H, 13C 1D and 2D; HRESIMS), as well as by comparison of the spectral data with those reported in the literature. Of note, compounds 2, 3, 4, 5, 6, 7, 8 and 9 were reported for the first time. All isolated compounds showed cytotoxicity against the human cancer cell lines U373 (glioblastoma) and MCF7 (breast) with IC50 values in a range of 1.78 - 40.14 μg/mL. The higher cytotoxic effect of compounds 1, 2 and 3 was also shown by MTT assay using additional cancer cell lines A549 (lung), PC-3 (prostate) and non-tumourigenic HUVEC and human breast MCF10 cells. Compound 1 was the most potent inhibitor of human cancer cell viability, follow by compounds 2 and 1 respectively. Compounds 1 and 2 induced apoptosis through mitochondrial permeabilization and caspase activation while compound 3 acted on cell fate via caspase-independent/non-apoptotic mechanisms, likely involving mitochondrial dysfunctions and aberrant generation of reactive oxygen species (ROS). Finally, in silico modelling and molecular approaches suggested that all molecules inhibit XIAP by binding to XIAP-BIR3 domain. The results confirm the therapeutic potential of isolated compounds from P. eriopodon and demonstrates that XIAP is a key determinant of tumor control, at the molecular crossroad of caspase-dependent/independent cell death pathways. |
| publishDate |
2020 |
| dc.date.accessioned.spa.fl_str_mv |
2020-07-24T16:54:26Z |
| dc.date.available.spa.fl_str_mv |
2020-07-24T16:54:26Z |
| dc.date.issued.spa.fl_str_mv |
2020-07-23 |
| dc.type.spa.fl_str_mv |
Trabajo de grado - Doctorado |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
| dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
| dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_db06 |
| dc.type.content.spa.fl_str_mv |
Text |
| format |
http://purl.org/coar/resource_type/c_db06 |
| status_str |
acceptedVersion |
| dc.identifier.citation.spa.fl_str_mv |
Muñoz, D & Cuca, L. (2020). Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica. Universidad Nacional de Colombia, Bogotá, Colombia. |
| dc.identifier.uri.none.fl_str_mv |
https://repositorio.unal.edu.co/handle/unal/77848 |
| identifier_str_mv |
Muñoz, D & Cuca, L. (2020). Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica. Universidad Nacional de Colombia, Bogotá, Colombia. |
| url |
https://repositorio.unal.edu.co/handle/unal/77848 |
| dc.language.iso.spa.fl_str_mv |
spa |
| language |
spa |
| dc.relation.references.spa.fl_str_mv |
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Atribución-NoComercial 4.0 InternacionalDerechos reservados - Universidad Nacional de ColombiaAcceso abiertohttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Cuca Suarez, Luis Enrique37a99195-fb27-461b-8816-f2919eecd27cMuñoz Cendales, Diego Ricardoa2e5c6d0-0190-4030-a490-9636c674897cQuímica de Productos Naturales Vegetales Bioactivos2020-07-24T16:54:26Z2020-07-24T16:54:26Z2020-07-23Muñoz, D & Cuca, L. (2020). Estudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxica. Universidad Nacional de Colombia, Bogotá, Colombia.https://repositorio.unal.edu.co/handle/unal/77848The cytotoxic effect of different Colombian Piper plants was determined by the MTT assay in human cancer cell lines A549 (lung), PC-3 (prostate) and MDAMB-231 (breast). The most potent cytotoxic effect was found in the leaves ethanolic extract of P. eriopodon with IC50 values less than 25 μg/mL. After different chromatographic techniques, nine alkenylphenols (1 - 9) were isolated from the ethanolic extract of leaves from P. eriopodon and their molecular structures were identified by the analysis of the spectroscopic data (IR; NMR 1H, 13C 1D and 2D; HRESIMS), as well as by comparison of the spectral data with those reported in the literature. Of note, compounds 2, 3, 4, 5, 6, 7, 8 and 9 were reported for the first time. All isolated compounds showed cytotoxicity against the human cancer cell lines U373 (glioblastoma) and MCF7 (breast) with IC50 values in a range of 1.78 - 40.14 μg/mL. The higher cytotoxic effect of compounds 1, 2 and 3 was also shown by MTT assay using additional cancer cell lines A549 (lung), PC-3 (prostate) and non-tumourigenic HUVEC and human breast MCF10 cells. Compound 1 was the most potent inhibitor of human cancer cell viability, follow by compounds 2 and 1 respectively. Compounds 1 and 2 induced apoptosis through mitochondrial permeabilization and caspase activation while compound 3 acted on cell fate via caspase-independent/non-apoptotic mechanisms, likely involving mitochondrial dysfunctions and aberrant generation of reactive oxygen species (ROS). Finally, in silico modelling and molecular approaches suggested that all molecules inhibit XIAP by binding to XIAP-BIR3 domain. The results confirm the therapeutic potential of isolated compounds from P. eriopodon and demonstrates that XIAP is a key determinant of tumor control, at the molecular crossroad of caspase-dependent/independent cell death pathways.En este trabajo, se evaluó el efecto citotóxico de diferentes especies colombianas del género Piper, por medio del ensayo del MTT en líneas celulares de cáncer humano A549 (pulmón), PC-3 (próstata) y MDA-MB-231 (mama). El extracto etanólico de hojas de P. eriopodon presentó el mayor efecto citotóxico con valores de IC50 por debajo de 25 μg/mL; y su fraccionamiento llevó al aislamiento de nueve compuestos (1-9) de tipo alquenilfenol. Los compuestos 2, 3, 4, 5, 6, 7, 8 y 9 son reportados por primera vez y sus estructuras químicas fueron establecidas por medio del análisis detallado de sus datos espectroscópicos (IR; RMN 1H, 13C 1D y 2D, HRESIMS) y la comparación con los datos reportados en la literatura. Todos los compuestos aislados mostraron tener propiedades citotóxicas en líneas celulares de cáncer humano U373 (glioblastoma) y MCF7 (mama) con valores de IC50 en un rango de 1.78 a 40.14 μg/mL. Los compuestos 1, 2 y 3 presentaron el efecto citotóxico más potente y fueron adicionalmente evaluados en células tumorales A549 (pulmón) y PC-3 (próstata), así como en células no tumorales HUVEC y MCF10. El compuesto 3 fue el inhibidor más potente en la viabilidad celular, seguido de los compuestos 2 y 1 respectivamente. Adicionalmente, se determinó que los compuestos 1 y 2 inducen apoptosis por medio de permeabilización mitocondrial y activación de caspasas, mientras que el compuesto 3 induce muerte celular independiente de caspasas que involucra disfunción mitocondrial y una producción aberrante de especies reactivas de oxígeno (ROS). Finalmente, se realizaron estudios in silico con el fin de evaluar el potencial efecto antagonista sobre la proteína XIAP, encontrando que los tres compuestos evaluados podrían unirse al dominio BIR3 de la proteína XIAP. Estos resultados confirman el potencial farmacológico que tienen los compuestos aislados de P. eriopodon y permiten demostrar el papel fundamental que tiene la proteína XIAP en el control de tumores, proporcionando información importante sobre la participación de XIAP en mecanismos de muerte celular tanto dependientes como independientes de caspasas.ColcienciasConvocatoria Nacional para estudios de Doctorado en Colombia "Francisco José de Caldas" No 528 de 2011Línea de Investigación: Bioprospección en agentes terapéuticosDoctorado167application/pdfspa540 - Química y ciencias afinesCáncerApoptosisMuerte independiente de caspasasXIAPAlquenilfenolesPiper eriopodonCancerApoptosisCaspase independent cell deathXIAPAlkenylphenolsPiper eriopodonEstudio fitoquímico de la especie vegetal Piper eriopodon y determinación de su actividad citotóxicaTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_db06TextBogotá - Ciencias - Doctorado en Ciencias - QuímicaDepartamento de QuímicaUniversidad Nacional de Colombia - Sede BogotáShen, B. 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Cell Biol. 2017, 19 (9), 1116–1129.ORIGINAL80040049.2020.pdf80040049.2020.pdfapplication/pdf40180711https://repositorio.unal.edu.co/bitstream/unal/77848/1/80040049.2020.pdf21161d32bcea22d5f0340dbf27f3f7b8MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8701https://repositorio.unal.edu.co/bitstream/unal/77848/3/license_rdf42fd4ad1e89814f5e4a476b409eb708cMD53LICENSElicense.txtlicense.txttext/plain; charset=utf-83991https://repositorio.unal.edu.co/bitstream/unal/77848/2/license.txt6f3f13b02594d02ad110b3ad534cd5dfMD52THUMBNAIL80040049.2020.pdf.jpg80040049.2020.pdf.jpgGenerated Thumbnailimage/jpeg5304https://repositorio.unal.edu.co/bitstream/unal/77848/4/80040049.2020.pdf.jpg9bb68c89b72d919f941d4d22a664cf92MD54unal/77848oai:repositorio.unal.edu.co:unal/778482023-07-12 23:03:21.2Repositorio Institucional Universidad Nacional de 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