Effects of flavonoids with anti-tumoral activity on the expression of receptors associated with EGFR activity in breast cancer cells

CEBRÓN JR; BOJORGE MA; MARDER M; MIQUET JG ; GONZÁLEZ L

Mar del plata

Congreso; LXIV Reunión anual de la Sociedad Argentina de Investigaciones Clínicas (SAIC); 2019

Sociedad Argentina de Investigación Clínica

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 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 (p0.05); while incubation with 2´-nitroflavone resulted in a diminution of ErbB2 (p0.05) 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 (p0.05). 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 (p0.05). 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.