Naringenin in combination with quercetin/fisetin shows synergistic anti-proliferative and migration reduction effects in breast cancer cell lines.

Abstract

Breast cancer is one of the most common cancers with a high mortality rate among women worldwide. Quercetin/fisetin and naringenin, three well-known flavonoids, have been used to fight against various cancers. The aim of the present study was to investigate the possible synergism of quercetin/fisetin with naringenin on MCF7 and MDA-MB-231 breast cancer cell lines. In this study, cultured MCF7 and MDA-MB-231 cells were treated with different concentrations of quercetin/fisetin individually and in combination with naringenin. MTT assay and scratch assay was employed to determine cell viability and migration respectively. Real-time PCR was used to study the expression level of apoptosis genes and miR-1275 (tumor suppressor miRNA) and mir-27a-3p (oncogenic miRNA). A synergism effect of quercetin/fisetin and naringenin (CI < 1) was observed for both cell lines. Combination therapies were significantly more effective in cell growth reduction, migration suppression and apoptosis induction than single therapies. Gene expression analysis revealed the upregulation of miR-1275 and downregulation miR-27a-3p. Our results indicate that quercetin/fisetin enhances the anti-proliferative and anti-migratory activities in combination with naringenin in MCF7 and MDA-MB-231 human breast cancer cell lines. Therefore, the combination of Que/Fis and Nar can be proposed as a promising therapeutic strategy for further investigations.