BCR-ABL1: Un blanco terapéutico modulado por extractos de plantas ¿Es beneficiosa su combinación con  imatinib?

Arango Forero, Ana María

Publicación:
BCR-ABL1: Un blanco terapéutico modulado por extractos de plantas ¿Es beneficiosa su combinación con imatinib?

dc.contributor.advisor	Arévalo Olaya. Cindy
dc.contributor.advisor	Fiorentino Gómez. Susana
dc.contributor.author	Arango Forero, Ana María
dc.date.accessioned	2026-03-18T20:22:14Z
dc.date.issued	2025
dc.description.abstract	El cáncer se origina por alteraciones genéticas que favorecen la proliferación celular descontrolada y la resistencia a la apoptosis. En neoplasias hematológicas, el oncogén BCR-ABL1 es clave, y su estudio ha llevado al desarrollo de inhibidores de tirosina quinasa como imatinib. No obstante, la resistencia a estos tratamientos sigue siendo un reto clínico. En este contexto, los extractos naturales representan una alternativa terapéutica prometedora. Este estudio evaluó el efecto de cuatro extractos vegetales (Esperanza de Petiveria alliacea, P2Et de Caesalpinia spinosa, Tillandsia usneoides y Piper nigrum) sobre la expresión de BCR-ABL1 en células K562, su posible interacción con la proteína ABL1 y su influencia sobre la actividad citotóxica de imatinib. La qPCR mostró que Esperanza, P2Et y P. nigrum reducen significativamente la expresión del oncogén. Los análisis in silico no revelaron interacciones directas con ABL1, pero sí con proteínas clave como p53 y ATM. Los ensayos de sinergia indicaron un efecto antagónico al combinar Esperanza, P2Et y Tillandsia usneoides con imatinib, mientras que Piper nigrum mostró un efecto aditivo. Estos hallazgos sugieren que los extractos pueden modular vías moleculares relevantes en leucemia, y destacan a P. nigrum como un posible agente coadyuvante en terapias combinadas con imatinib.
dc.description.degreelevel	Pregrado
dc.description.degreename	Bacteriólogo(a) y Laboratorista Clínico
dc.format.extent	21p.
dc.format.mimetype	application/pdf
dc.identifier.uri	https://repositorio.universidadmayor.edu.co/handle/unicolmayor/7328
dc.language.iso	spa
dc.publisher	Universidad Colegio Mayor de Cundinamarca
dc.publisher.faculty	Facultad de Ciencias de la Salud
dc.publisher.place	Bogota
dc.publisher.program	Bacteriología y Laboratorio Clínico
dc.relation.references	Hanahan D. Hallmarks of Cancer: New Dimensions. Vol. 12, Cancer Discovery. 2022.
dc.relation.references	Brown G. Oncogenes, Proto-Oncogenes, and Lineage Restriction of Cancer Stem Cells. Int J Mol Sci [Internet]. 2021;22(18). Available from: https://www.mdpi.com/1422-0067/22/18/9667
dc.relation.references	Kontomanolis EN, Koutras A, Syllaios A, Schizas D, Mastoraki A, Garmpis N, et al. Role of oncogenes and tumor-suppressor genes in carcinogenesis: A review. Vol. 40, Anticancer Research. 2020.
dc.relation.references	Grzes M, Oron M, Staszczak Z, Jaiswar A, Nowak-Niezgoda M, Walerych D. A driver never works alone—interplay networks of mutant p53, MYC, RAS, and other universal oncogenic drivers in human cancer. Vol. 12, Cancers. 2020.
dc.relation.references	Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Vol. 36, Leukemia. 2022.
dc.relation.references	Komorowski L, Fidyt K, Patkowska E, Firczuk M. Philadelphia chromosome-positive leukemia in the lymphoid lineage—similarities and differences with the myeloid lineage and specific vulnerabilities. Vol. 21, International Journal of Molecular Sciences. 2020.
dc.relation.references	El-Tanani M, Nsairat H, Matalka II, Lee YF, Rizzo M, Aljabali AA, et al. The impact of the BCR-ABL oncogene in the pathology and treatment of chronic myeloid leukemia. Vol. 254, Pathology Research and Practice. 2024.
dc.relation.references	Amarante-Mendes GP, Rana A, Datoguia TS, Hamerschlak N, Brumatti G. BCR-ABL1 Tyrosine Kinase Complex Signaling Transduction: Challenges to Overcome Resistance in Chronic Myeloid Leukemia. Pharmaceutics. 2022;14(1).
dc.relation.references	Nisar S, Hashem S, Macha MA, Yadav SK, Muralitharan S, Therachiyil L, et al. Exploring Dysregulated Signaling Pathways in Cancer. Curr Pharm Des. 2020;26(4).
dc.relation.references	Grassi S, Palumbo S, Mariotti V, Liberati D, Guerrini F, Ciabatti E, et al. The WNT pathway is relevant for the BCR-ABL1-independent resistance in chronic myeloid leukemia. Front Oncol. 2019;9.
dc.relation.references	Pottier C, Fresnais M, Gilon M, Jérusalem G, Longuespée R, Sounni NE. Tyrosine kinase inhibitors in cancer: Breakthrough and challenges of targeted therapy. Vol. 12, Cancers. 2020.
dc.relation.references	Upadhyay V, Raval A, Shah K, Shah FD, Rawal R. A Prognostic and Predictive Study of BCR-ABL Expression Based on Characterization of Fusion Transcripts. Indian Journal of Clinical Biochemistry. 2020;35(1).
dc.relation.references	Yang Y, Li S, Wang Y, Zhao Y, Li Q. Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective. Vol. 7, Signal Transduction and Targeted Therapy. 2022.
dc.relation.references	Yang Y, Li S, Wang Y, Zhao Y, Li Q. Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective. Vol. 7, Signal Transduction and Targeted Therapy. 2022.
dc.relation.references	Braun TP, Eide CA, Druker BJ. Response and Resistance to BCR-ABL1-Targeted Therapies. Vol. 37, Cancer Cell. 2020.
dc.relation.references	Braun TP, Eide CA, Druker BJ. Response and Resistance to BCR-ABL1-Targeted Therapies. Vol. 37, Cancer Cell. 2020.
dc.relation.references	Shyam Sunder S, Sharma UC, Pokharel S. Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management. Vol. 8, Signal Transduction and Targeted Therapy. 2023.
dc.relation.references	Pezzani R, Salehi B, Vitalini S, Iriti M, Zuñiga FA, Sharifi‐Rad J, et al. Synergistic effects of plant derivatives and conventional chemotherapeutic agents: An update on the cancer perspective. Vol. 55, Medicina (Lithuania). 2019.
dc.relation.references	Chandra S, Gahlot M, Choudhary AN, Palai S, de Almeida RS, de Vasconcelos JEL, et al. Scientific evidences of anticancer potential of medicinal plants. Vol. 2, Food Chemistry Advances. 2023.
dc.relation.references	Singh A, Prakash A, Choudhary R. Bioactive Components Having Antimicrobial and Anticancerous Properties: A Review. In: Bioactive Components: A Sustainable System for Good Health and Well- Being. 2022.
dc.relation.references	Siddiqui AJ, Jahan S, Singh R, Saxena J, Ashraf SA, Khan A, et al. Plants in Anticancer Drug Discovery: From Molecular Mechanism to Chemoprevention. Vol. 2022, BioMed Research International. 2022.
dc.relation.references	Situmorang PC, Ilyas S, Nugraha SE, Syahputra RA, Nik Abd Rahman NMA. Prospects of compounds of herbal plants as anticancer agents: a comprehensive review from molecular pathways. Vol. 15, Frontiers in Pharmacology. Frontiers Media SA; 2024.
dc.relation.references	Shrihastini V, Muthuramalingam P, Adarshan S, Sujitha M, Chen JT, Shin H, et al. Plant derived bioactive compounds, their anti‐cancer effects and in silico approaches as an alternative target treatment strategy for breast cancer: An updated overview. Vol. 13, Cancers. 2021.
dc.relation.references	Maher T, Raus RA, Daddiouaissa D, Ahmad F, Adzhar NS, Latif ES, et al. Medicinal plants with anti- leukemic effects: A review. Vol. 26, Molecules. 2021.
dc.relation.references	Horvath Z, Saiko P, Illmer C, Madlener S, Hoechtl T, Bauer W, et al. Synergistic action of resveratrol, an ingredient of wine, with Ara-C and tiazofurin in HL-60 human promyelocytic leukemia cells. Exp Hematol. 2005;33(3).
dc.relation.references	Chang YS, Lu KH, Lee HJ, Huang ML, Lai SC, Ho YL, et al. Synergistic apoptosis-inducing antileukemic effects of arsenic trioxide and mucuna macrocarpa stem extract in human leukemic cells via a reactive oxygen species-dependent mechanism. Evidence-based Complementary and Alternative Medicine. 2012;2012.
dc.relation.references	Dai H, Deng HB, Wang YH, Guo JJ. Resveratrol inhibits the growth of gastric cancer via the wnt/β- catenin pathway. Oncol Lett. 2018;16(2).
dc.relation.references	Silva JPB, Do Nascimento SCM, Okabe DH, Pinto ACG, De Oliveira FR, Da Paixão TP, et al. Antimicrobial and anticancer potential of Petiveria alliacea L. (Herb to “Tame the Master”): A review. Vol. 12, Pharmacognosy Reviews. 2018.
dc.relation.references	Rojas L, Pardo-Rodriguez D, Urueña C, Lasso P, Arévalo C, Cala MP, et al. Effect of Petiveria alliacea Extracts on Metabolism of K562 Myeloid Leukemia Cells. Int J Mol Sci. 2023 Dec 1;24(24).
dc.relation.references	Hernández JF, Urueña CP, Cifuentes MC, Sandoval TA, Pombo LM, Castañeda D, et al. A Petiveria alliacea standardized fraction induces breast adenocarcinoma cell death by modulating glycolytic metabolism. J Ethnopharmacol. 2014;153(3).
dc.relation.references	Hernández JF, Urueña CP, Sandoval TA, Cifuentes MC, Formentini L, Cuezva JM, et al. A cytotoxic Petiveria alliacea dry extract induces ATP depletion and decreases β-F1-ATPase expression in breast cancer cells and promotes survival in tumor-bearing mice. Revista Brasileira de Farmacognosia. 2017;27(3).
dc.relation.references	Arévalo C, Carlosama C, Rojas L, Cala MP, Hamon MP, Friguet B, et al. Modulation of Tumor Metabolism in Acute Leukemia by Plant-Derived Polymolecular Drugs and Their Effects on Mitochondrial Function. Molecules [Internet]. 2025 Apr 16;30(8):1783. Available from: https://www.mdpi.com/1420-3049/30/8/1783
dc.relation.references	Murillo N, Lasso P, Urueña C, Pardo-Rodriguez D, Ballesteros-Ramírez R, Betancourt G, et al. Petiveria alliacea Reduces Tumor Burden and Metastasis and Regulates the Peripheral Immune Response in a Murine Myeloid Leukemia Model. Int J Mol Sci [Internet]. 2023 [cited 2025 Jan 16];2023:12972. Available from: https://doi.org/10.3390/ijms241612972
dc.relation.references	Urueña C, Mancipe J, Hernandez J, Castañeda D, Pombo L, Gomez A, et al. Gallotannin-rich Caesalpinia spinosa fraction decreases the primary tumor and factors associated with poor prognosis in a murine breast cancer model. BMC Complement Altern Med. 2013;13.
dc.relation.references	Prieto K, Cao Y, Mohamed E, Trillo-Tinoco J, Sierra RA, Urueña C, et al. Polyphenol-rich extract induces apoptosis with immunogenic markers in melanoma cells through the ER stress-associated kinase PERK. Cell Death Discov. 2019;5(1).
dc.relation.references	Arévalo Olaya CM. Evaluación del efecto de los fitomedicamentos derivados de Caesalpinia spinosa y Petiveria alliacea en el metabolismo energético en diferentes modelos celulares [Internet]. 2024. Available from: http://hdl.handle.net/10554/68693
dc.relation.references	Ballesteros-Ramírez R, Durán MI, Fiorentino S. Genotoxicity and mutagenicity assessment of a standardized extract (P2Et) obtained from Caesalpinia spinosa. Toxicol Rep. 2021;8.
dc.relation.references	Lasso P, Rojas L, Arévalo C, Urueña C, Murillo N, Barreto A, et al. Tillandsia usneoides Extract Decreases the Primary Tumor in a Murine Breast Cancer Model but Not in Melanoma. Cancers (Basel). 2022;14(21).
dc.relation.references	Rojas L, Lasso P, Murillo N, Costa GM, Fiorentino S. Chemical composition and biological activity of ethanolic leaf extract from Tillandsia usneoides in a murine model of acute myeloid leukemia. Advances in Traditional Medicine. 2025;
dc.relation.references	Arévalo CM, Cruz-Rodriguez N, Quijano S, Fiorentino S. Plant-derived extracts and metabolic modulation in leukemia: a promising approach to overcome treatment resistance. Vol. 10, Frontiers in Molecular Biosciences. 2023.
dc.relation.references	Lasso P, Rojas L, Arévalo C, Urueña C, Murillo N, Nossa P, et al. Piper nigrum extract suppresses tumor growth and enhances the antitumor immune response in murine models of breast cancer and melanoma. Cancer Immunology, Immunotherapy. 2023;72(10).
dc.relation.references	K-562 - CCL-243 \| ATCC [Internet]. [cited 2025 Jan 16]. Available from: https://www.atcc.org/products/ccl-243
dc.relation.references	PROYECTO DE PROSPECTO Novartis GLIVEC ® IMATINIB Comprimidos recubiertos.
dc.relation.references	Savage DG, Antman KH. Imatinib Mesylate — A New Oral Targeted Therapy. New England Journal of Medicine. 2002;346(9).
dc.relation.references	Prieto K, Arévalo C, Lasso P, Carlosama C, Urueña C, Fiorentino S, et al. Plant extracts modulate cellular stress to inhibit replication of mouse Coronavirus MHV-A59. Heliyon. 2024;10(1).
dc.relation.references	Sandoval Medina TA. Evaluación de la actividad antitumoral de la fracción p2et obtenida de caesalpinia spinosa y los compuestos aislados de la misma, en el control de las células madre tumorales en un modelo de cáncer de seno metastásico [Internet]. Pontificia Universidad Javeriana; 2016. Available from: http://hdl.handle.net/10554/19652
dc.relation.references	von Mering C, Jensen LJ, Snel B, Hooper SD, Krupp M, Foglierini M, et al. STRING: Known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res. 2005 Jan 1;33(DATABASE ISS.).
dc.relation.references	Bhanumathy KK, Balagopal A, Vizeacoumar FS, Vizeacoumar FJ, Freywald A, Giambra V. Review protein tyrosine kinases: Their roles and their targeting in leukemia. Cancers (Basel). 2021;13(2).
dc.relation.references	Qian S, Wei Z, Yang W, Huang J, Yang Y, Wang J. The role of BCL-2 family proteins in regulating apoptosis and cancer therapy. Vol. 12, Frontiers in Oncology. 2022.
dc.relation.references	Kruiswijk F, Labuschagne CF, Vousden KH. p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat Rev Mol Cell Biol [Internet]. 2015;16(7):393–405. Available from: https://doi.org/10.1038/nrm4007
dc.relation.references	Roberts NJ, Klein AP. Genome-wide sequencing to identify the cause of hereditary cancer syndromes: With examples from familial pancreatic cancer. Cancer Lett [Internet]. 2013;340(2):227–33. Available from: https://www.sciencedirect.com/science/article/pii/S0304383512006556
dc.relation.references	Castañeda DM, Pombo LM, Urueña CP, Hernandez JF, Fiorentino S. A gallotannin-rich fraction from Caesalpinia spinosa (Molina) Kuntze displays cytotoxic activity and raises sensitivity to doxorubicin in a leukemia cell line. BMC Complement Altern Med. 2012;12.
dc.relation.references	Chi HT, Ly BTK. Artemisia vulgaris inhibits BCR/ABL and promotes apoptosis in chronic myeloid leukemia cells. Biomed Rep. 2022;17(6).
dc.relation.references	Guo Y, Li Y, Shan Q, He G, Lin J, Gong Y. Curcumin potentiates the anti-leukemia effects of imatinib by downregulation of the AKT/mTOR pathway and BCR/ABL gene expression in Ph+ acute lymphoblastic leukemia. International Journal of Biochemistry and Cell Biology. 2015;65.
dc.relation.references	Ly BTK, Chi HT, Yamagishi M, Kano Y, Hara Y, Nakano K, et al. Inhibition of FLT3 Expression by Green Tea Catechins in FLT3 Mutated-AML Cells. PLoS One. 2013;8(6).
dc.relation.references	Tisi R, Gaponenko V, Vanoni M, Sacco E. Natural products attenuating biosynthesis, processing, and activity of ras oncoproteins: State of the art and future perspectives. Vol. 10, Biomolecules. 2020.
dc.relation.references	Ahmadu AA, Delehouzé C, Haruna A, Mustapha L, Lawal BA, Udobre A, et al. Betulin, a newly characterized compound in acacia auriculiformis bark, is a multi-target protein kinase inhibitor. Molecules. 2021;26(15).
dc.relation.references	Sarno F, Pepe G, Termolino P, Carafa V, Massaro C, Merciai F, et al. Trifolium Repens blocks proliferation in chronic myelogenous leukemia via the BCR-ABL/STAT5 pathway. Cells. 2020;9(2).
dc.relation.references	Aki T, Uemura K. Cell death and survival pathways involving ATM protein kinase. Vol. 12, Genes. 2021.
dc.relation.references	Sullivan KD, Palaniappan V V, Espinosa JM. ATM regulates cell fate choice upon p53 activation by modulating mitochondrial turnover and ROS levels. Cell Cycle. 2015;14(1).
dc.relation.references	Charoensedtasin K, Kheansaard W, Roytrakul S, Tanyong D. Piperine, a black pepper compound, induces autophagy and cellular senescence mediated by NF-κB and IL-6 in acute leukemia. BMC Complement Med Ther. 2024 Dec 1;24(1):343.
dc.relation.references	Yin Z, Huang G, Gu C, Liu Y, Yang J, Fei J. Discovery of Berberine that Targetedly Induces Autophagic Degradation of both BCR-ABL and BCR-ABL T315I through Recruiting LRSAM1 for Overcoming Imatinib Resistance. Clinical Cancer Research. 2020;26(15).
dc.relation.references	Arévalo-Ferrin JJ, García-Ortiz JA, Arévalo-Olaya CM, Quijano-Gómez SM, Fiorentino-Gómez S, Rodríguez-Pardo VM. Plant-derived extracts P2Et and Anamu-SC affect NO and ROS levels in leukemic cells. Univ Sci (Bogota). 2023;28(2).
dc.relation.references	Prieto K, Lozano MP, Urueña C, Alméciga-Díaz CJ, Fiorentino S, Barreto A. The delay in cell death caused by the induction of autophagy by P2Et extract is essential for the generation of immunogenic signals in melanoma cells. Apoptosis. 2020;25(11–12).
dc.rights	Al consultar y hacer uso de este recurso, está aceptando las condiciones de uso establecidas por los autores.
dc.rights.license	Atribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)
dc.rights.uri	https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subject.proposal	Oncogén
dc.subject.proposal	Extractos naturales
dc.subject.proposal	imatinib
dc.title	BCR-ABL1: Un blanco terapéutico modulado por extractos de plantas ¿Es beneficiosa su combinación con imatinib?	spa
dc.type	Trabajo de grado - Pregrado
dc.type.coar	http://purl.org/coar/resource_type/c_7a1f
dc.type.coarversion	http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.content	Text
dc.type.driver	info:eu-repo/semantics/bachelorThesis
dc.type.redcol	http://purl.org/redcol/resource_type/TP
dc.type.version	info:eu-repo/semantics/publishedVersion
dspace.entity.type	Publication

Archivos

Bloque original

Mostrando 1 - 3 de 3

Nombre:: 4 (1). VF BCR-ABL1- Un blanco terapeutico modulado por extractos de plantas ¿Es beneficiosa su combinacioìn con imatinib
Tamaño:: 1.59 MB
Formato:: Unknown data format

Descargar