The flavones induce breast cancer cell apoptosis via activation Foxo3a

Abstract

Flavonoids constitute the largest and most important group of polyphenolic compounds in plants. Flavonoids possess numerous beneficial biological properties including antiallergic, antiviral, anti‐inflammatory, antioxidation, and antitumor activities. More importantly, flavones are good candidates of antitumor agents by inducing apoptosis in various types of human cancers. In this study, we investigated the effects of the flavone, apigenin, and luteolin on the growth of breast cancer cells. The results showed that flavonoids significantly decreased the viability of MCF‐7 cells. Flavonoids‐induced apoptosis in MCF‐7 cells was confirmed by Hoechst33342 staining and induction of sub‐G1 phase by flow cytometry. Flavonoids‐treated MCF‐7 cells were arrested at G1and S phase, which was associated with a marked increment of the expression of p21and p27 protein. The induction of p21 and p27 appeared to be transcriptionally upregulated and was p53‐dependent. Next, we use microarray to determine the flavonoids‐induced‐apoptosis regulated genes. Our results revealed flavonoids will increase the expression level of FOXO3a. FOXO3a, one of large forkhead family members, play a pivotal role in the regulation of a myriad of cellular functions including cell cycle arrest and cell death from stress stimuli. To further investigate its mechanism of action, we treated MCF‐7 cells with flavones and showed increase in nuclear localization of FOXO3a, which coincided with decreased Akt signaling activity. Taken together, the data show that cell death of breast cancer cells in response to flavones is dependent upon FOXO3a activation resulting in Akt inhibition.