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Research article Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells

机译:研究文章人参皂苷衍生物1C对前列腺癌细胞的抗癌活性及其潜在机制

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Background AD-2 (20( R )-dammarane-3b, 12b, 20, 25-tetrol; 25-OH-PPD) is a ginsenoside and isolated from Panax ginseng , showing anticancer activity against extensive human cancer cell lines. In this study, effects and mechanisms of 1C ((20 R )-3b- O -(L-alanyl)-dammarane-12b, 20, 25-triol), a modified version of AD-2, were evaluated for its development as a novel anticancer drug. Methods MTT assay was performed to evaluate cell cytotoxic activity. Cell cycle and levels of reactive oxygen species (ROS) were determined using flow cytometry analysis. Western blotting was employed to analyze signaling pathways. Results 1C concentration-dependently reduces prostate cancer cell viability without affecting normal human gastric epithelial cell line-1 viability. In LNCaP prostate cancer cells, 1C triggered apoptosis via Bcl-2 family-mediated mitochondria pathway, downregulated expression of mouse double minute 2, upregulated expression of p53 and stimulated ROS production. ROS scavenger, N-acetylcysteine, can attenuate 1C-induced apoptosis. 1C also inhibited the proliferation of LNCaP cells through inhibition on Wnt/β-catenin signaling pathway. Conclusion 1C shows obvious anticancer activity based on inducing cell apoptosis by Bcl-2 family-mediated mitochondria pathway and ROS production, inhibiting Wnt/β-catenin signaling pathway. These findings demonstrate that 1C may provide leads as a potential agent for cancer therapy.
机译:背景技术AD-2(20(R)-dammarane-3b,12b,20,25-tetrol; 25-OH-PPD)是人参皂苷,从人参中分离出来,显示出对广泛的人类癌细胞系的抗癌活性。在这项研究中,对1C((20 R)-3b- O-(L-丙氨酰基)-dammarane-12b,20,25-triol)(AD-2的改良版)的作用和机理进行了评估,其方法如下:一种新的抗癌药。方法采用MTT法检测细胞的细胞毒活性。使用流式细胞仪分析确定细胞周期和活性氧水平(ROS)。使用蛋白质印迹法分析信号传导途径。结果1C浓度依赖性地降低了前列腺癌细胞的活力,而不影响正常人胃上皮细胞系1的活力。在LNCaP前列腺癌细胞中,1C通过Bcl-2家族介导的线粒体途径触发细胞凋亡,下调小鼠双分2的表达,上调p53的表达并刺激ROS的产生。 ROS清除剂N-乙酰半胱氨酸可以减弱1C诱导的细胞凋亡。 1C还通过抑制Wnt /β-catenin信号传导途径抑制LNCaP细胞的增殖。结论1C具有明显的抗癌活性,这是由于Bcl-2家族介导的线粒体途径和ROS产生诱导细胞凋亡,抑制Wnt /β-catenin信号通路。这些发现表明1C可能提供潜在的癌症治疗药物。

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