CONICET | Buscador de Institutos y Recursos Humanos

Flavonoids have been associated with a reduced incidence of cancer. For that reason, they were proposed as chemopreventive and chemotherapeutic agents per se or in combination with traditional antitumoral drugs. Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor associated with tumorigenesis of several tissues. It was proposed to be involved in the molecular mechanism of action of several flavonoids. With the aim of investigating if a combinatory therapy involving flavones and EGFR inhibitors would be a possible effective treatment for breast cancer, the present study analyzes if flavones with breast cancer antitumoral actions -2´-nitroflavone and apigenin- modulate EGFR expression or the expression of receptors that interact or modulate EGFR activity. For that purpose, MDA-MB-231 breast cancer cells were stimulated with 2´-nitroflavone or apigenin at two different concentrations (a concentration close to the IC50 and a higher one) for 48 hs. Assays were performed in absence or presence of 10% fetal bovine serum. Afterwards, the protein content of EGFR, ErbB2, Met and IGF-IR were assessed by immunoblotting. Besides, PARP cleavage and phosphorylation of p38 were determined. Results showed that incubation with apigenin induced a reduction in EGFR and ErbB2 protein expression; while incubation with 2´-nitroflavone resulted in a diminution of ErbB2 depending on the experimental condition, but no conclusive effects on EGFR content were observed. 2´-nitroflavone caused a reduction in the expression of IGF-IR and Met. Apigenin also induced a decline in Met content but only when cells were incubated in absence of serum. In addition, an increment in p38 phosphorylation and PARP cleavage were observed in both treatments. In conclusion, the flavones demonstrated to have effects on the expression of receptors associated with EGFR activity which could justify a possible combinatory therapy involving flavones and EGFR inhibitors.