Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells
Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells
Xu De Wang(Shenyang Pharmaceutical University); Guang Yue Su(Shenyang Pharmaceutical University); Chen Zhao(Shenyang Pharmaceurical University); Fan Zhi Qu(Shenyang Pharmaceurical University); Peng Wang(Shenyang Pharmaceurical University); Yuqing Zhao(Shenyang Pharmaceutical University)
42권 2호, 133~143쪽
초록
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/b-catenin signaling pathway. Conclusion: 1C shows obvious anticancer activity based on inducing cell apoptosis by Bcl-2 familymediated mitochondria pathway and ROS production, inhibiting Wnt/b-catenin signaling pathway. These findings demonstrate that 1C may provide leads as a potential agent for cancer therapy.
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/b-catenin signaling pathway. Conclusion: 1C shows obvious anticancer activity based on inducing cell apoptosis by Bcl-2 familymediated mitochondria pathway and ROS production, inhibiting Wnt/b-catenin signaling pathway. These findings demonstrate that 1C may provide leads as a potential agent for cancer therapy.
- 발행기관:
- 고려인삼학회
- 분류:
- 기타의약학