Caracterización del efecto de mezclas de terpenos derivados de aceites esenciales de Lippia alba y agentes quimioterapéuticos sobre células de cáncer hematológico

Digital

Autores:: Vargas Munévar, Laura Camila

Tipo de recurso:: Trabajo de grado de pregrado

Fecha de publicación:: 2020

Institución:: Universidad de Santander

Repositorio:: Repositorio Universidad de Santander

Idioma:: spa

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dc.title.spa.fl_str_mv	Caracterización del efecto de mezclas de terpenos derivados de aceites esenciales de Lippia alba y agentes quimioterapéuticos sobre células de cáncer hematológico
title	Caracterización del efecto de mezclas de terpenos derivados de aceites esenciales de Lippia alba y agentes quimioterapéuticos sobre células de cáncer hematológico
spellingShingle	Caracterización del efecto de mezclas de terpenos derivados de aceites esenciales de Lippia alba y agentes quimioterapéuticos sobre células de cáncer hematológico Aceites esenciales Interacciones farmacológicas Cáncer hematológico Lippia alba Essential oils Pharmacologic interactions Hematologic cancer
title_short	Caracterización del efecto de mezclas de terpenos derivados de aceites esenciales de Lippia alba y agentes quimioterapéuticos sobre células de cáncer hematológico
title_full	Caracterización del efecto de mezclas de terpenos derivados de aceites esenciales de Lippia alba y agentes quimioterapéuticos sobre células de cáncer hematológico
title_fullStr	Caracterización del efecto de mezclas de terpenos derivados de aceites esenciales de Lippia alba y agentes quimioterapéuticos sobre células de cáncer hematológico
title_full_unstemmed	Caracterización del efecto de mezclas de terpenos derivados de aceites esenciales de Lippia alba y agentes quimioterapéuticos sobre células de cáncer hematológico
title_sort	Caracterización del efecto de mezclas de terpenos derivados de aceites esenciales de Lippia alba y agentes quimioterapéuticos sobre células de cáncer hematológico
dc.creator.fl_str_mv	Vargas Munévar, Laura Camila
dc.contributor.advisor.none.fl_str_mv	Moreno Moreno, Erika Marcela
dc.contributor.author.none.fl_str_mv	Vargas Munévar, Laura Camila
dc.subject.proposal.spa.fl_str_mv	Aceites esenciales Interacciones farmacológicas Cáncer hematológico
topic	Aceites esenciales Interacciones farmacológicas Cáncer hematológico Lippia alba Essential oils Pharmacologic interactions Hematologic cancer
dc.subject.proposal.eng.fl_str_mv	Lippia alba Essential oils Pharmacologic interactions Hematologic cancer
description	Digital
publishDate	2020
dc.date.issued.none.fl_str_mv	2020-03-13
dc.date.accessioned.none.fl_str_mv	2021-08-20T21:34:06Z
dc.date.available.none.fl_str_mv	2021-08-20T21:34:06Z 2022-12-31
dc.type.spa.fl_str_mv	Trabajo de grado - Pregrado
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dc.rights.spa.fl_str_mv	Derechos Reservados - Universidad de Santander, 2020
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dc.format.extent.spa.fl_str_mv	142 p
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dc.publisher.spa.fl_str_mv	Bucaramanga : Universidad de Santander, 2020
dc.publisher.faculty.spa.fl_str_mv	Facultad de Ciencias Exactas, Naturales y Agropecuarias
dc.publisher.place.spa.fl_str_mv	Bucaramanga, Colombia
dc.publisher.program.spa.fl_str_mv	Microbiología Industrial
institution	Universidad de Santander
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spelling	Moreno Moreno, Erika Marcela9f50910e-4e7d-4b84-b369-774ac0f07d44-1Vargas Munévar, Laura Camila161af28f-fbe0-4d4e-b1ac-60ac314e4e27-12021-08-20T21:34:06Z2022-12-312021-08-20T21:34:06Z2020-03-13DigitalEl cáncer constituye la segunda causa de muerte a nivel mundial, siendo las leucemias el tipo de cáncer hematológico más representativo en niños y adultos, con una cifra aproximada de 309.006 defunciones y 437.033 nuevos diagnósticos. Actualmente, el tratamiento de estas neoplasias se caracteriza por ser altamente tóxico, con desenlace en múltiples y graves efectos colaterales. Por tanto, el desarrollo de terapias farmacológicas basadas en moléculas bioactivas de plantas es prometedor teniendo en cuenta sus propiedades antiproliferativas y baja toxicidad. En este contexto, este trabajo caracterizó el efecto de mezclas de terpenos, derivados de aceites esenciales de Lippia alba, limoneno y citral, con los medicamentos oncológicos citarabina y doxorrubicina. Los resultados obtenidos de las interacciones farmacológicas fueron expresados por medio de isobologramas de radio fijo y la detección de cambios morfológicos y de potencial de membrana mitocondrial fue llevado a cabo por medio de microscopía óptica y de fluorescencia, respectivamente. En este trabajo, se encontró que en células de LMA la combinación con mejor perfil fue limoneno+citarabina (ΣCIF=0,27), demostrando además efecto antagónico (protector) sobre el linaje no tumoral (ΣCIF=1,15). Por otra parte, en células de LMC, la mejor interacción fue limoneno+citral (ΣCIF=0,46); sin embargo, es importante destacar que la mezcla citral+doxorrubicina, representó la segunda combinación de mayor eficacia (ΣCIF=0,54) y, además, evidenció un efecto antagonista sobre las células Vero (ΣCIF =1,18). En todas las combinaciones testadas se evidenciaron cambios morfológicos posiblemente de tipo apoptótico. Estos resultados permiten sugerir que las moléculas bioactivas podrían ser utilizadas como coadyuvantes de la terapia convencional, potencializando su efecto antiproliferativo de manera selectiva contra células de la LMA y LMC.Cancer constitutes the second cause of death worldwide, with leukemia being the most representative hematologic type of cancer in children and adults, with nearly 309006 deceases and 437033 new diagnoses, just in 2018. Therefore, the development of pharmacologic therapy based on bioactive molecules from plants is promising due to its antiproliferative properties and low toxicity. This research characterized the effect of terpenes mixtures, derivates of Lippia alba essential oil, limonene and citral, with the oncologic medications, Cytarabine and Doxorubicin. The results obtained, were given by fixed-radio isobolograms and the morphologic and potential variations of the mitochondrial membrane were detected by optical and fluorescence microscopy. It was found in AML cells that, the combination with the best profile was limonene+Cytarabine (ΣCIF=0.27), proving in addition, its antagonist effect on the non-tumoral lineage (ΣCIF=1.15). On the other hand, the cells in CML showed the best interaction with limonene+citral (ΣCIF=0.46), however, it is essential to emphasize that, the citral+doxorubicin displayed the second combination with the greatest effectiveness (ΣCIF=0.54), besides, this combination presented antagonist effect on Vero cells (ΣCIF = 1.18). All the tested combinations demonstrated morphologic changes related with a possible apoptosis induction. These results allow to suggest that the bioactive molecules could be used in the development of a co-adjuvant therapy of the conventional chemotherapeutics proving promising antineoplastic and selective characteristics in the treatment of AML and CML.PregradoMicrobiólogo Industrial1 ed.Introducción .............................................................................................................................. 16 1. Planteamiento del problema .................................................................................................. 20 1.1 Pregunta problema ........................................................................................................... 23 2. Justificación .......................................................................................................................... 24 3. Hipótesis ............................................................................................................................... 30 3.1 Hipótesis alterna .............................................................................................................. 30 3.2 Hipótesis nula .................................................................................................................. 30 4. Objetivos ............................................................................................................................... 31 4.1 Objetivo general .............................................................................................................. 31 4.2 Objetivos específicos ....................................................................................................... 31 5. Marco teórico ........................................................................................................................ 32 5.1 Cáncer ............................................................................................................................. 32 5.1.1 Epidemiología ........................................................................................................... 35 5.2 Leucemia ......................................................................................................................... 38 5.2.1 Epidemiología ........................................................................................................... 39 5.2.2 Factores de riesgo ...................................................................................................... 40 5.2.2.1 Radiación. .......................................................................................................... 40 5.2.2.2 Pesticidas. .......................................................................................................... 42 5.2.2.3 Benceno. ............................................................................................................ 43 5.2.2.4 Predisposición genética. ..................................................................................... 45 5.2.2.5 Agentes infecciosos............................................................................................ 46 5.3 Leucemia mieloide aguda (LMA) .................................................................................... 47 5.3.1 Epidemiología ........................................................................................................... 48 5.3.2 Factores predisponentes ............................................................................................. 49 5.3.3 Manifestaciones clínicas y diagnóstico ...................................................................... 50 5.3.4 Tratamiento convencional ......................................................................................... 51 5.4 Leucemia mieloide crónica (LMC) .................................................................................. 54 5.4.1 Epidemiología ........................................................................................................... 55 5.4.2 Factores predisponentes ............................................................................................. 55 5.4.3 Manifestaciones clínicas y diagnóstico ...................................................................... 56 5.4.4 Tratamiento convencional ......................................................................................... 57 5.5 Lippia alba (Mill.) N.E. Brown ........................................................................................ 58 5.5.1 Quimiotipos............................................................................................................... 60 5.5.2 Aceites esenciales ...................................................................................................... 63 5.5.3 Factores que afectan la composición y producción de los AEs ................................... 67 5.5.3.1 Genética. ............................................................................................................ 67 5.5.3.2 Ataque de patógenos. ......................................................................................... 67 5.5.3.3 Factores ambientales. ......................................................................................... 68 5.5.3.4 Estrés Hídrico. ................................................................................................... 69 5.5.3.5 Nutrición de la planta. ........................................................................................ 69 5.5.4 Terpenos ................................................................................................................... 71 5.5.4.1 Biosíntesis.......................................................................................................... 71 5.5.5 D-Limoneno .............................................................................................................. 73 5.5.6 Citral ......................................................................................................................... 74 6. Marco Referencial ................................................................................................................. 76 7. Materiales y Metodos ............................................................................................................ 81 7.1 Materiales ........................................................................................................................ 81 7.1.1 Cultivos Celulares ..................................................................................................... 81 7.1.2 Terpenos y medicamentos ......................................................................................... 82 7.2 Métodos ........................................................................................................................... 82 7.2.1 Matriz de Interacciones farmacológicas ..................................................................... 82 7.2.2 Citotoxicidad en Células Vero ................................................................................... 84 7.2.3 Actividad antiproliferativa sobre los linajes leucémicos ............................................. 85 7.2.4 Cambios Morfológicos detectados por microscopía óptica ......................................... 85 7.2.5 Detección del potencial de membrana mitocondrial ................................................... 85 7.2.6 Análisis de datos ....................................................................................................... 86 7.2.7 Consideraciones éticas ............................................................................................... 86 8. Resultados ............................................................................................................................. 87 8.1 Actividad antiproliferativa y citotóxica sobre las células DA-3 ........................................ 87 8.1.1 Cambios morfológicos y potencial de membrana mitocondrial sobre DA-3 ............... 89 8.2 Actividad antiproliferativa y citotóxica sobre K562 ......................................................... 91 8.2.1 Cambios morfológicos y potencial de membrana mitocondrial sobre K562 ............... 93 9. Discusión .............................................................................................................................. 96 10. Conclusiones ..................................................................................................................... 103 11. Recomendaciones .............................................................................................................. 104 Referencias Bibliográficas....................................................................................................... 105142 papplication/pdfT 33.20 V173chttps://repositorio.udes.edu.co/handle/001/5529spaBucaramanga : Universidad de Santander, 2020Facultad de Ciencias Exactas, Naturales y AgropecuariasBucaramanga, ColombiaMicrobiología IndustrialDerechos Reservados - Universidad de Santander, 2020info:eu-repo/semantics/closedAccessAtribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)https://creativecommons.org/licenses/by-nc-nd/4.0/http://purl.org/coar/access_right/c_14cbAceites esencialesInteracciones farmacológicasCáncer hematológicoLippia albaEssential oilsPharmacologic interactionsHematologic cancerCaracterización del efecto de mezclas de terpenos derivados de aceites esenciales de Lippia alba y agentes quimioterapéuticos sobre células de cáncer hematológicoTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1fTextinfo:eu-repo/semantics/bachelorThesishttps://purl.org/redcol/resource_type/TPhttp://purl.org/coar/version/c_71e4c1898caa6e32Todas las AudienciasAbdelmajeed, N. 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D., Fritschi, L., Infante-Rivard, C., Glass, D. C., Miligi, L., Dockerty, J. D., Schüz, J. (2014). Parental occupational pesticide exposure and the risk of childhood leukemia in the offspring: findings from the childhood leukemia international consortium. International journal of cancer, 135(9), 2157–2172. doi:10.1002/ijc.28854Banjar, H., Adelson, D., Brown, F., & Chaudhri, N. (2017). Intelligent Techniques Using Molecular Data Analysis in Leukaemia: An Opportunity for Personalized Medicine Support System. BioMed research international, 2017, 3587309. https://doi.org/10.1155/2017/3587309Bartikova, H., Hanusova, V., Skalova, L., Ambroz, M., & Bousova, I. (2014). Antioxidant, pro-oxidant and other biological activities of sesquiterpenes. Current topics in medicinal chemistry, 14(22), 2478–2494. https://doi.org/10.2174/1568026614666141203120833Bavaro, L., Martelli, M., Cavo, M., & Soverini, S. (2019). 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Anticancer research, 33(3), 929-940. https://europepmc.org/article/med/23482764PublicationORIGINALCaracterizacióndelefectodemezclasdeterpenosderivadosdeaceitesesencialesdeLippiaalbayagentesquimioterapéuticossobrecélulasdecáncer.pdfCaracterizacióndelefectodemezclasdeterpenosderivadosdeaceitesesencialesdeLippiaalbayagentesquimioterapéuticossobrecélulasdecáncer.pdfapplication/pdf2054732https://repositorio.udes.edu.co/bitstreams/eb0117e9-de9c-4535-a84b-7b1c97dff482/downloadf24e49676cb149113d50ab7e574ef9b7MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-859https://repositorio.udes.edu.co/bitstreams/593147c1-a215-4c25-82b3-11e59e6e9bc0/download38d94cf55aa1bf2dac1a736ac45c881cMD52TEXTCaracterizacióndelefectodemezclasdeterpenosderivadosdeaceitesesencialesdeLippiaalbayagentesquimioterapéuticossobrecélulasdecáncer.pdf.txtCaracterizacióndelefectodemezclasdeterpenosderivadosdeaceitesesencialesdeLippiaalbayagentesquimioterapéuticossobrecélulasdecáncer.pdf.txtExtracted texttext/plain101958https://repositorio.udes.edu.co/bitstreams/d6bb1602-ebba-4bbc-9ef4-463dcafa912b/download0d942e78ec77962f1a96a5e72c74b80bMD53THUMBNAILCaracterizacióndelefectodemezclasdeterpenosderivadosdeaceitesesencialesdeLippiaalbayagentesquimioterapéuticossobrecélulasdecáncer.pdf.jpgCaracterizacióndelefectodemezclasdeterpenosderivadosdeaceitesesencialesdeLippiaalbayagentesquimioterapéuticossobrecélulasdecáncer.pdf.jpgGenerated Thumbnailimage/jpeg6981https://repositorio.udes.edu.co/bitstreams/a91e6529-84c9-4c3a-a30e-f11c7990921a/download853805f3ae5d4dddd0fd3f3a522a39eeMD54001/5529oai:repositorio.udes.edu.co:001/55292022-10-25 09:56:04.156https://creativecommons.org/licenses/by-nc-nd/4.0/Derechos Reservados - Universidad de Santander, 2020https://repositorio.udes.edu.coRepositorio Universidad de Santandersoporte@metabiblioteca.comTGljZW5jaWEgZGUgUHVibGljYWNpw7NuIFVERVMKRGlyZWN0cmljZXMgZGUgVVNPIHkgQUNDRVNPCgo=

Caracterización del efecto de mezclas de terpenos derivados de aceites esenciales de Lippia alba y agentes quimioterapéuticos sobre células de cáncer hematológico

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