2. Academic Validation
  3. 2'-Nitroflavone targets PARP1 and alters cytoskeleton to inhibit triple-negative breast cancer progression

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

  • Sci Rep. 2026 Jan 3;16(1):4164. doi: 10.1038/s41598-025-34214-w.
Vanina S Vachetta 1 2,  Viviana C Blank 1 2,  Mariel Marder 1 2,  Melisa B Nicoud 3 4,  Jorge Cantero 5 6,  Miriam Benso 1 2,  Silvia Vanzulli 7,  María G Ortega 8,  Margot Paulino Zunini 5,  Vanina A Medina 3 4,  María T Elola # 1 2,  María F Troncoso # 9 10
Affiliations

Affiliations

  • 1 Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • 2 Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química y Fisicoquímica Biológicas (IQUIFIB) Prof. Alejandro C. Paladini, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • 3 Departamento de Fisicomatemática, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • 4 Laboratorio de Biología Tumoral e Inflamación, Facultad de Ciencias Médicas, Instituto de Investigaciones Biomédicas (BIOMED), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Pontificia Universidad Católica Argentina (UCA), 1107, Buenos Aires, Argentina.
  • 5 Centro de Bioinformática, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
  • 6 Centro de Investigaciones Médicas, Facultad de Ciencias de la Salud, Universidad Nacional del Este, Ciudad del Este, Paraguay.
  • 7 Instituto de Investigaciones Hematológicas (IIHEMA), Academia Nacional De Medicina, Buenos Aires, Argentina.
  • 8 Farmacognosia, Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Instituto Multidisciplinario de Biología Vegetal (IMBIV-CONICET), Ciudad Universitaria, Córdoba, Argentina.
  • 9 Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. mf.troncoso@ffyb.uba.ar.
  • 10 Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química y Fisicoquímica Biológicas (IQUIFIB) Prof. Alejandro C. Paladini, Universidad de Buenos Aires, Buenos Aires, Argentina. mf.troncoso@ffyb.uba.ar.
  • # Contributed equally.
PMID: 41484449 DOI: 10.1038/s41598-025-34214-w
Abstract

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.

Keywords

Apoptosis; Cytoskeleton alterations; Flavonoid; Mitotic catastrophe; PARP1 interaction; Triple-negative breast cancer.

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