2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression

Autores: Vachetta, Vanina S.; Blank, Viviana C.; Marder, Mariel; Nicoud, Melisa Beatriz; Cantero, Jorge; Benso, Miriam; Vanzulli, Silvia; Ortega, María G.; Paulino Zunini, Margot; Medina, Vanina Araceli; Elola, María T.; Troncoso, María F.
Año de publicación: 2026
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: Fil: Vachetta, Vanina S. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Blank, Viviana C. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Nicoud, Melisa B. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cantero, Jorge. Universidad Nacional del Este; Paraguay
Fil: Benso, Miriam. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina
Fil: Vanzulli, Silvia. Academia Nacional de Medicina; Argentina
Fil: Ortega, María G. Universidad Nacional de Córdoba; Argentina
Fil: Paulino Zunini, Margot. Universidad de la República; Uruguay
Fil: Medina, Vanina A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Tumoral e Inflamación; Argentina
Fil: Elola, María T. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Troncoso, María F. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Triple-negative breast cancer (TNBC) is an aggressive subtype, often resistant to chemotherapy. Flavonoids are polyphenolic compounds that exhibit anticancer properties. In this study, the potential antitumor effects of the synthetic flavonoid 2’-nitroflavone (2'NF) in TNBC were investigated. Our in vitro results show that 2’NF reduces TNBC cell viability, proliferation, and survival, while inducing cell cycle arrest, apoptosis, and mitotic catastrophe. Additionally, 2'NF inhibits TNBC and endothelial cell migration, likely due to severe disruptions in tubulin and actin cytoskeletons. Computational analysis revealed that 2’NF has a favorable pharmacological profile as a potential drug candidate. In a murine TNBC model, 2'NF administration slowed tumor growth without evident toxicity. Mechanistic in silico studies propose that poly(ADP-ribose) polymerase-1 (PARP1), a key enzyme involved in DNA repair, may be a target of 2’NF. Molecular docking and dynamics simulations demonstrated the formation of a thermodynamically stable complex between 2’NF and the catalytic domain of PARP1. Moreover, in vitro PARP enzymatic activity was inhibited by 2’NF in TNBC cells. These promising findings suggest the potential of 2’NF as a novel PARP1 inhibitor or a scaffold for developing improved inhibitors, offering new avenues for combination therapies in TNBC treatment.
Fuente: Scientific Reports, vol. 16, art. 4164
Materia: CANCER DE MAMA
BIOQUIMICA
CANCER DE MAMA TRIPLE NEGATIVO
FLAVONOIDES
TRATAMIENTO ANTITUMORAL
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
Institución: Pontificia Universidad Católica Argentina
OAI Identificador: oai:ucacris:123456789/22004

Acceder

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oai_identifier_str	oai:ucacris:123456789/22004
network_acronym_str	RIUCA
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network_name_str	Repositorio Institucional (UCA)
spelling	2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progressionVachetta, Vanina S.Blank, Viviana C.Marder, MarielNicoud, Melisa BeatrizCantero, JorgeBenso, MiriamVanzulli, SilviaOrtega, María G.Paulino Zunini, MargotMedina, Vanina AraceliElola, María T.Troncoso, María F.CANCER DE MAMABIOQUIMICACANCER DE MAMA TRIPLE NEGATIVOFLAVONOIDESTRATAMIENTO ANTITUMORALFil: Vachetta, Vanina S. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Blank, Viviana C. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Nicoud, Melisa B. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Cantero, Jorge. Universidad Nacional del Este; ParaguayFil: Benso, Miriam. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Vanzulli, Silvia. Academia Nacional de Medicina; ArgentinaFil: Ortega, María G. Universidad Nacional de Córdoba; ArgentinaFil: Paulino Zunini, Margot. Universidad de la República; UruguayFil: Medina, Vanina A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Tumoral e Inflamación; ArgentinaFil: Elola, María T. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Troncoso, María F. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaTriple-negative breast cancer (TNBC) is an aggressive subtype, often resistant to chemotherapy. Flavonoids are polyphenolic compounds that exhibit anticancer properties. In this study, the potential antitumor effects of the synthetic flavonoid 2’-nitroflavone (2'NF) in TNBC were investigated. Our in vitro results show that 2’NF reduces TNBC cell viability, proliferation, and survival, while inducing cell cycle arrest, apoptosis, and mitotic catastrophe. Additionally, 2'NF inhibits TNBC and endothelial cell migration, likely due to severe disruptions in tubulin and actin cytoskeletons. Computational analysis revealed that 2’NF has a favorable pharmacological profile as a potential drug candidate. In a murine TNBC model, 2'NF administration slowed tumor growth without evident toxicity. Mechanistic in silico studies propose that poly(ADP-ribose) polymerase-1 (PARP1), a key enzyme involved in DNA repair, may be a target of 2’NF. Molecular docking and dynamics simulations demonstrated the formation of a thermodynamically stable complex between 2’NF and the catalytic domain of PARP1. Moreover, in vitro PARP enzymatic activity was inhibited by 2’NF in TNBC cells. These promising findings suggest the potential of 2’NF as a novel PARP1 inhibitor or a scaffold for developing improved inhibitors, offering new avenues for combination therapies in TNBC treatment.Nature Portfolio2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/220042045-232210.1038/s41598-025-34214-wScientific Reports, vol. 16, art. 4164reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2026-09-28T11:10:45Zoai:ucacris:123456789/22004instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852026-09-28 11:10:45.664Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse
dc.title.none.fl_str_mv	2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression
title	2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression
spellingShingle	2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression Vachetta, Vanina S. CANCER DE MAMA BIOQUIMICA CANCER DE MAMA TRIPLE NEGATIVO FLAVONOIDES TRATAMIENTO ANTITUMORAL
title_short	2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression
title_full	2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression
title_fullStr	2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression
title_full_unstemmed	2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression
title_sort	2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression
dc.creator.none.fl_str_mv	Vachetta, Vanina S. Blank, Viviana C. Marder, Mariel Nicoud, Melisa Beatriz Cantero, Jorge Benso, Miriam Vanzulli, Silvia Ortega, María G. Paulino Zunini, Margot Medina, Vanina Araceli Elola, María T. Troncoso, María F.
author	Vachetta, Vanina S.
author_facet	Vachetta, Vanina S. Blank, Viviana C. Marder, Mariel Nicoud, Melisa Beatriz Cantero, Jorge Benso, Miriam Vanzulli, Silvia Ortega, María G. Paulino Zunini, Margot Medina, Vanina Araceli Elola, María T. Troncoso, María F.
author_role	author
author2	Blank, Viviana C. Marder, Mariel Nicoud, Melisa Beatriz Cantero, Jorge Benso, Miriam Vanzulli, Silvia Ortega, María G. Paulino Zunini, Margot Medina, Vanina Araceli Elola, María T. Troncoso, María F.
author2_role	author author author author author author author author author author author
dc.subject.none.fl_str_mv	CANCER DE MAMA BIOQUIMICA CANCER DE MAMA TRIPLE NEGATIVO FLAVONOIDES TRATAMIENTO ANTITUMORAL
topic	CANCER DE MAMA BIOQUIMICA CANCER DE MAMA TRIPLE NEGATIVO FLAVONOIDES TRATAMIENTO ANTITUMORAL
dc.description.none.fl_txt_mv	Fil: Vachetta, Vanina S. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Blank, Viviana C. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Nicoud, Melisa B. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Cantero, Jorge. Universidad Nacional del Este; Paraguay Fil: Benso, Miriam. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Vanzulli, Silvia. Academia Nacional de Medicina; Argentina Fil: Ortega, María G. Universidad Nacional de Córdoba; Argentina Fil: Paulino Zunini, Margot. Universidad de la República; Uruguay Fil: Medina, Vanina A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Biología Tumoral e Inflamación; Argentina Fil: Elola, María T. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Troncoso, María F. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Triple-negative breast cancer (TNBC) is an aggressive subtype, often resistant to chemotherapy. Flavonoids are polyphenolic compounds that exhibit anticancer properties. In this study, the potential antitumor effects of the synthetic flavonoid 2’-nitroflavone (2'NF) in TNBC were investigated. Our in vitro results show that 2’NF reduces TNBC cell viability, proliferation, and survival, while inducing cell cycle arrest, apoptosis, and mitotic catastrophe. Additionally, 2'NF inhibits TNBC and endothelial cell migration, likely due to severe disruptions in tubulin and actin cytoskeletons. Computational analysis revealed that 2’NF has a favorable pharmacological profile as a potential drug candidate. In a murine TNBC model, 2'NF administration slowed tumor growth without evident toxicity. Mechanistic in silico studies propose that poly(ADP-ribose) polymerase-1 (PARP1), a key enzyme involved in DNA repair, may be a target of 2’NF. Molecular docking and dynamics simulations demonstrated the formation of a thermodynamically stable complex between 2’NF and the catalytic domain of PARP1. Moreover, in vitro PARP enzymatic activity was inhibited by 2’NF in TNBC cells. These promising findings suggest the potential of 2’NF as a novel PARP1 inhibitor or a scaffold for developing improved inhibitors, offering new avenues for combination therapies in TNBC treatment.
description	Fil: Vachetta, Vanina S. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas; Argentina
publishDate	2026
dc.date.none.fl_str_mv	2026
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://repositorio.uca.edu.ar/handle/123456789/22004 2045-2322 10.1038/s41598-025-34214-w
url	https://repositorio.uca.edu.ar/handle/123456789/22004
identifier_str_mv	2045-2322 10.1038/s41598-025-34214-w
dc.language.none.fl_str_mv	eng
language	eng
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv	openAccess
rights_invalid_str_mv	https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Nature Portfolio
publisher.none.fl_str_mv	Nature Portfolio
dc.source.none.fl_str_mv	Scientific Reports, vol. 16, art. 4164 reponame:Repositorio Institucional (UCA) instname:Pontificia Universidad Católica Argentina
reponame_str	Repositorio Institucional (UCA)
collection	Repositorio Institucional (UCA)
instname_str	Pontificia Universidad Católica Argentina
repository.name.fl_str_mv	Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina
repository.mail.fl_str_mv	claudia_fernandez@uca.edu.ar
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score	13.265058

2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression

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