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Published on: June 9, 2023
Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway
Chia-Hung Lin1, Ching-Yao Chang2, Kuan-Rong Lee3
1Institute of Molecular Medicine, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, 30013, Taiwan. james07212001@yahoo.com.tw.
Background:
Flavones 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.
Methods:
The 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.
Results:
Flavone, 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.
Conclusion:
Taken 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.
Insights
Flavone, apigenin, and luteolin show potent anti-cancer effects against human breast cancer cells. These natural compounds induce apoptosis and cell cycle arrest by inhibiting PI3K/Akt and activating FOXO3a signaling pathways.
Area of Science:
- Natural Products Chemistry
- Molecular Biology
- Cancer Research
Background:
- Flavones, plant-derived compounds, exhibit diverse biological activities, including anti-tumor properties.
- This study focuses on the anti-cancer potential of specific flavones: flavone, apigenin, and luteolin.
Purpose of the Study:
- To investigate the anti-tumor effects of flavone, apigenin, and luteolin on human breast cancer cell lines.
- To elucidate the molecular mechanisms underlying their anti-cancer activity.
Main Methods:
- Cell proliferation was assessed using the MTS assay.
- Apoptosis was analyzed via Hoechst 33342 staining, flow cytometry, and western blotting.
- Cell migration and signaling pathways were determined using real-time cell analysis, qPCR, and western blotting.
Main Results:
- Flavone, apigenin, and luteolin significantly inhibited breast cancer cell proliferation in a dose- and time-dependent manner.
- These compounds induced apoptosis and cell cycle arrest (sub-G1 phase).
- Inhibition of Phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB)/Akt signaling and subsequent activation of forkhead box O3 (FOXO3a) were observed, leading to increased expression of p21 and p27.
Conclusions:
- Flavone, apigenin, and luteolin demonstrate significant anti-cancer activity against breast cancer cells.
- The mechanism involves cell cycle arrest and apoptosis induction via PI3K/Akt inhibition and FOXO3a activation.
- These flavones represent promising candidates for breast cancer prevention and treatment.
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