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

  • Wang, Xu De (School of Functional Food and Wine, Shenyang Pharmaceutical University) ;
  • Su, Guang Yue (School of Functional Food and Wine, Shenyang Pharmaceutical University) ;
  • Zhao, Chen (Key Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceurical University) ;
  • Qu, Fan Zhi (School of Functional Food and Wine, Shenyang Pharmaceutical University) ;
  • Wang, Peng (School of Functional Food and Wine, Shenyang Pharmaceutical University) ;
  • Zhao, Yu Qing (School of Functional Food and Wine, Shenyang Pharmaceutical University)
  • Received : 2016.06.29
  • Accepted : 2016.12.26
  • Published : 2018.04.15

Abstract

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 ((20R)-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 $Wnt/{\beta}-catenin$ signaling pathway. Conclusion: 1C shows obvious anticancer activity based on inducing cell apoptosis by Bcl-2 family-mediated mitochondria pathway and ROS production, inhibiting $Wnt/{\beta}-catenin$ signaling pathway. These findings demonstrate that 1C may provide leads as a potential agent for cancer therapy.

Keywords

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