Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway.
Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway.
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DOI：
10.1186/s12885-015-1965-7
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发表时间：
2015-12-16
期刊：
影响因子：
3.8
通讯作者：
Wan L
中科院分区：
文献类型：
--
作者：
Lin CH;Chang CY;Lee KR;Lin HJ;Chen TH;Wan L
黄酮类化合物具有抗过敏、抗病毒、抗炎、抗氧化、抗肿瘤等多种生物活性。本研究探讨了黄酮、芹菜素和木犀草素对人乳腺癌细胞的抗肿瘤作用。采用MTS法研究了黄酮、芹菜素和木犀草素的抗癌活性。Hoechst 33342染色、流式细胞术和western blot检测细胞凋亡。使用培养插入物和配备有CIM板16的xCELLigence实时细胞分析仪测定细胞迁移。采用实时荧光定量PCR和Western blot方法检测黄酮、芹菜素和木犀草素诱导的信号通路。黄酮、芹菜素和木犀草素对乳腺癌细胞株Hs 578 T、MDA-MB-231和MCF-7的增殖有明显的抑制作用，且呈浓度和时间依赖性。通过Hoechst 33342染色和诱导细胞周期亚G1期证实黄酮、芹菜素和木犀草素通过凋亡抑制乳腺癌细胞生长的能力。黄酮、芹菜素和木犀草素通过抑制磷酸肌醇3-激酶（PI 3 K）和蛋白激酶B（PKB）/Akt诱导FOXO 3a表达。这随后提高了FOXO 3a靶基因的表达，包括细胞周期蛋白依赖性激酶抑制剂p21 Cip 1（p21）和p27 kip 1（p27），这增加了活化的聚（ADP）聚合酶（PARP）和细胞色素c的水平。这些结果表明，黄酮、芹菜素和木犀草素通过抑制PI 3 K/Akt活化和增强FOXO 3a活化诱导乳腺癌细胞周期阻滞和凋亡，提示黄酮、芹菜素和木犀草素有望成为防治乳腺癌的潜在药物。
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. 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. 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. 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.