Abstract
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.
Highlights
Flavones found in plants display various biological activities, including anti-allergic, anti-viral, anti-inflammatory, anti-oxidation, and anti-tumor effects
Apigenin and luteolin on cell viability and apoptosis of breast cancer cells To determine the effect of the flavone, apigenin, and luteolin on MCF-7, Hs578T, MDA-MB-231 cancer cells and on a non-tumorigenic MCF-10A cell, a MTS/ PMS assay was performed
Cell migration was measured in real time, and treatment with flavone, apigenin, and luteolin decreased the migration ability of MCF-7 cell (Fig. 3c)
Summary
Flavones found in plants display various biological activities, including anti-allergic, anti-viral, anti-inflammatory, anti-oxidation, and anti-tumor effects. We investigated the anti-tumor effects of flavone, apigenin and luteolin on human breast cancer cells. Despite the new promising breakthrough in therapeutics, the annual breast cancer mortality rate continues to increase, and one million new cases are diagnosed every year [1]. Breast cancer develops as a consequence of cellular changes that increase the rate of cell division and. FOXO transcription factors are involved in the cellular stress response, and they regulate cell cycle progression and apoptosis [15]. FOXO3a plays a vital role in the initiation of cell cycle arrest, in addition to its involvement in DNA damage-mediated apoptosis [16]. Several anti-cancer drugs have been shown to increase the expression of FOXO3a, which suggest it is a tangible therapeutic target for breast cancer therapy [17]
Published Version (Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have