Background and Aims: Naringenin (NAR) is a natural flavonoid monomer, which has been proven to have anti-cancer effects against ovarian cancer, rectal cancer, and lung cancer. However, its effect on breast cancer is unclear. Therefore, this study was conducted to observe the effect of NAR on the proliferation, migration, invasion and apoptosis in breast cancer cells from different species, and preliminarily analyze the mechanism, so as to provide theoretical and experimental basis for the development of relevant drugs for breast cancer. 
Methods: The in vitro cultured human breast cancer MCF-7 cells and mouse breast cancer 4T1 cells were uses as study objects. The two types of cells were divided into two concentrations (100–200 μg/mL) of NAR treatment groups and control group, respectively, and the cells in control group were treated with DMSO. The changes in cell viabilities after above treatment for different times (24, 48 and 72 h) were measured by CCK-8 assay. The colony formation, migration and invasion abilities and apoptosis after above treatment for 24 h were detected by colony-forming assay, cell scratch assay, Transwell invasion assay and Hoechst apoptosis staining assay, respectively, and the expressions of Akt, the apoptosis- and cell cycle-related proteins and the endothelial-mesenchymal transition (EMT)-related molecules were determined by Western blot analysis.
Results: Compared with corresponding control group, the cell viabilities in the two types of breast cancer cells were significantly decreased after NAR treatment, with a certain time and concentration dependence (all P<0.01). Compared with corresponding control group, the relative colony formation rates, wound healing rates and the number of invading cells were significantly reduced, while the apoptotic rates were significantly increased in the two types of breast cancer cells after NAR treatment (all P<0.01); the protein expressions of Akt, Bcl-2, CDK4, cyclin D1, and MMP-9 were significantly down-regulated, while the Bax expressions were significantly up-regulated (all P<0.01).
Conclusion: NAR can effectively inhibit the proliferation, migration and invasion while promote apoptosis in both human breast cancer cells and mouse breast cancer cells. The mechanism may be related to its inhibiting the Akt pathway and regulating the cell cycle and the EMT process.