a Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of education, Molecular Medicine Research Center, College of Pharmacy , Yanbian University , Yanji , China.
Immunopharmacol Immunotoxicol. 2017 Dec;39(6):338-347. doi: 10.1080/08923973.2017.1371187. Epub 2017 Sep 7.
Amorfrutin A is a natural product isolated from the fruits of Amorpha fruticosa L. and has been shown to exhibit multiple bioeffector functions. In the present study, we investigated whether amorfrutin A exerts anticancer effects by inhibiting STAT3 activation in cervical cancer cells.
To investigate the effectiveness of amorfrutin A as a treatment of cancer, and determine the underlying pharmacological mechanism of action.
HeLa, SK-Hep1, MDA-MB-231 and HCT116 cells were used in this study. Major assays were luciferase reporter assay, MTT, Western blot analysis, immunofluorescence assay, reverse transcription-PCR (RT-PCR), flow cytometric analysis, EdU labeling and immunofluorescence, xenografted assay.
Amorfrutin A significantly inhibited tumor necrosis factor-α (TNF-α)-induced phosphorylation and nuclear translocation of STAT3 in human cervical carcinoma cells. Amorfrutin A also inhibited activation of the upstream kinases Janus-activated kinase 1 (JAK1), JAK2 and Src signaling pathways. Furthermore, amorfrutin A increased the expression of p53, p21, p27, induced cell cycle arrest in the G1 phase as well as decreased levels of various oncogene protein products. In vivo studies further confirmed the inhibitory effect of amorfrutin A on the expression of STAT3 proteins, leading to a decrease growth of HeLa cells in a xenograft tumor model.
The results indicated that amorfrutin A is a potent inhibitor of STAT3 and provide new perspectives into the mechanism of its anticancer activity.
冬凌草甲素是从紫穗槐中分离得到的天然产物，具有多种生物效应功能。本研究旨在探讨冬凌草甲素是否通过抑制宫颈癌细胞 STAT3 激活发挥抗癌作用。
研究冬凌草甲素治疗癌症的效果，并确定其潜在的药理作用机制。
本研究使用了 HeLa、SK-Hep1、MDA-MB-231 和 HCT116 细胞。主要检测方法包括荧光素酶报告基因检测、MTT、Western blot 分析、免疫荧光分析、逆转录聚合酶链反应（RT-PCR）、流式细胞术分析、EdU 标记和免疫荧光、异种移植实验。
冬凌草甲素显著抑制肿瘤坏死因子-α（TNF-α）诱导的人宫颈癌细胞中 STAT3 的磷酸化和核转位。冬凌草甲素还抑制了 Janus 激活激酶 1（JAK1）、JAK2 和Src 信号通路的上游激酶的激活。此外，冬凌草甲素增加了 p53、p21、p27 的表达，诱导细胞周期停滞在 G1 期，并降低了各种癌基因蛋白产物的水平。体内研究进一步证实了冬凌草甲素对 STAT3 蛋白表达的抑制作用，导致 HeLa 细胞在异种移植肿瘤模型中的生长减少。
结果表明，冬凌草甲素是 STAT3 的有效抑制剂，为其抗癌活性的机制提供了新的视角。
