Inhibitory effects of 2′-nitroflavone and apigenin on EGFR signaling in breast cancer cells
- 1Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires
- 2Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires
Abstract
The epidermal growth factor receptor (EGFR) is frequently dysregulated in certain cancers, including breast cancer. Gefitinib, an EGFR tyrosine kinase inhibitor (TKI) used in non-small cell lung cancer, was proposed for breast cancer treatment. The use of TKI in combination with other compounds may improve therapy effectiveness and delay drug-resistance development. Since many flavonoids exhibit anticancer effects, their combination with EGFR inhibitors was suggested for the treatment of certain tumors. In the current work, we assessed the effects of apigenin and 2′-nitroflavone as monotherapy in hormone-sensitive (MCF-7) and triple negative (MDA-MB-231) breast cancer cells. These flavones inhibited cell growth and negatively modulated EGFR signaling. Since 2′-nitroflavone exhibited a higher potency, we evaluated the effect of a combined therapy with gefitinib. This treatment led to a stronger cell growth inhibition than drugs alone, with combination index values suggesting synergistic interactions, particularly at lower concentrations. An enhancement of the proapoptotic effect was also observed. Thus, 2′-nitroflavone and apigenin exerted antitumor effects in breast cancer cells that were mediated, at least in part, by negative modulation of EGFR signaling. Moreover, a synergistic growth inhibitory effect for the combination of 2′-nitroflavone with gefitinib was found, supporting further investigation of these compounds in preclinical models of breast cancer.
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BibTeX
@article{cebron2026inhibitory,
title = {{Inhibitory effects of 2′-nitroflavone and apigenin on EGFR signaling in breast cancer cells}},
author = {Julieta R. Cebrón and Belén E. Berin and Mariana A. Bojorge and Ana I. Sotelo and Diego A. Chiappetta and Mariel Marder and María F. Troncoso and Viviana C. Blank and Lorena González and Johanna G. Miquet},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-62101-5},
url = {https://doi.org/10.1038/s41598-026-62101-5},
note = {CC BY},
}
RIS
TY - JOUR
TI - Inhibitory effects of 2′-nitroflavone and apigenin on EGFR signaling in breast cancer cells
AU - Julieta R. Cebrón
AU - Belén E. Berin
AU - Mariana A. Bojorge
AU - Ana I. Sotelo
AU - Diego A. Chiappetta
AU - Mariel Marder
AU - María F. Troncoso
AU - Viviana C. Blank
AU - Lorena González
AU - Johanna G. Miquet
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-62101-5
UR - https://doi.org/10.1038/s41598-026-62101-5
AB - The epidermal growth factor receptor (EGFR) is frequently dysregulated in certain cancers, including breast cancer. Gefitinib, an EGFR tyrosine kinase inhibitor (TKI) used in non-small cell lung cancer, was proposed for breast cancer treatment. The use of TKI in combination with other compounds may improve therapy effectiveness and delay drug-resistance development. Since many flavonoids exhibit anticancer effects, their combination with EGFR inhibitors was suggested for the treatment of certain tumors. In the current work, we assessed the effects of apigenin and 2′-nitroflavone as monotherapy in hormone-sensitive (MCF-7) and triple negative (MDA-MB-231) breast cancer cells. These flavones inhibited cell growth and negatively modulated EGFR signaling. Since 2′-nitroflavone exhibited a higher potency, we evaluated the effect of a combined therapy with gefitinib. This treatment led to a stronger cell growth inhibition than drugs alone, with combination index values suggesting synergistic interactions, particularly at lower concentrations. An enhancement of the proapoptotic effect was also observed. Thus, 2′-nitroflavone and apigenin exerted antitumor effects in breast cancer cells that were mediated, at least in part, by negative modulation of EGFR signaling. Moreover, a synergistic growth inhibitory effect for the combination of 2′-nitroflavone with gefitinib was found, supporting further investigation of these compounds in preclinical models of breast cancer.
SN - 2045-2322
ER -