Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway

BMC Cancer

Research Article

Ching-Yao Chang¹  Lei Wan²  Hui-Ju Lin³  Ter-Hsin Chen⁴  Kuan-Rong Lee⁵  Chia-Hung Lin⁵ 

[1] Department of Biotechnology, Asia University, Taichung, Taiwan;Department of Biotechnology, Asia University, Taichung, Taiwan;School of Chinese Medicine, China Medical University, No. 91, Hsueh-Shih Road, 40402, Taichung, Taiwan;Department of Gynecology, China Medical University Hospital, Taichung, Taiwan;Department of Ophthalmology, China Medical University Hospital, Taichung, Taiwan;School of Chinese Medicine, China Medical University, No. 91, Hsueh-Shih Road, 40402, Taichung, Taiwan;Graduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan;Institute of Molecular Medicine, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, 30013, Hsinchu, Taiwan;

关键词: Breast cancer;    Flavones;    FOXO3a;    Akt;    p27;    Apoptosis;   

DOI  :  10.1186/s12885-015-1965-7

 received in 2015-05-14, accepted in 2015-11-30,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundFlavones found in plants display various biological activities, including anti-allergic, anti-viral, anti-inflammatory, anti-oxidation, and anti-tumor effects. In this study, we investigated the anti-tumor effects of flavone, apigenin and luteolin on human breast cancer cells.MethodsThe anti-cancer activity of flavone, apigenin and luteolin was investigated using the MTS assay. Apoptosis was analyzed by Hoechst 33342 staining, flow cytometry and western blot. Cell migration was determined using the culture inserts and xCELLigence real-time cell analyzer instrument equipped with a CIM-plate 16. Real-time quantitative PCR and western blot were used to determine the signaling pathway elicited by flavone, apigenin and luteolin.ResultsFlavone, apigenin and luteolin showed potent inhibitory effects on the proliferation of Hs578T, MDA-MB-231 and MCF-7 breast cancer cells in a concentration and time-dependent manner. The ability of flavone, apigenin and luteolin to inhibit the growth of breast cancer cells through apoptosis was confirmed by Hoechst33342 staining and the induction of sub-G1 phase of the cell cycle. Flavone, apigenin and luteolin induced forkhead box O3 (FOXO3a) expression by inhibiting Phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB)/Akt. This subsequently elevated the expression of FOXO3a target genes, including the Cyclin-dependent kinase inhibitors p21Cip1 (p21) and p27kip1 (p27), which increased the levels of activated poly(ADP) polymerase (PARP) and cytochrome c.ConclusionTaken together, these data demonstrated that flavone, apigenin and luteolin induced cell cycle arrest and apoptosis in breast cancer cells through inhibiting PI3K/Akt activation and increasing FOXO3a activation, which suggest that flavone, apigenin and luteolin will be the potential leads for the preventing and treating of breast cancer.

【 授权许可】

CC BY   
© Lin et al. 2015