Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells
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 ve...
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doaj-3e3fa436414e44abab8b178e51e9d9e52020-11-24T22:50:13ZengElsevierJournal of Ginseng Research1226-84532018-04-01422133143Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cellsXu De Wang0Guang Yue Su1Chen Zhao2Fan Zhi Qu3Peng Wang4Yu Qing Zhao5School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China; Key Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceurical University, Shenyang, ChinaSchool of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China; Key Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceurical University, Shenyang, ChinaKey Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceurical University, Shenyang, China; College of Life Science and Biological Pharmaceutical, Shenyang Pharmaceutical University, Shenyang, ChinaSchool of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China; Key Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceurical University, Shenyang, ChinaSchool of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China; Key Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceurical University, Shenyang, ChinaSchool of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China; Key Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceurical University, Shenyang, China; Corresponding author. School of Functional Food and Wine, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenhe District, Shenyang 110016, Liaoning, China; Key Laboratory of Structure-based Drug Design and Discovery of Education, Shenyang Pharmaceurical University, No. 103, Wenhua Road, Shenhe District, Shenyang 110016, Liaoning, China.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/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. Keywords: 1C, AD-2, apoptosis, reactive oxygen species, Wnt/β-catenin pathwayhttp://www.sciencedirect.com/science/article/pii/S1226845316301154 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xu De Wang Guang Yue Su Chen Zhao Fan Zhi Qu Peng Wang Yu Qing Zhao |
spellingShingle |
Xu De Wang Guang Yue Su Chen Zhao Fan Zhi Qu Peng Wang Yu Qing Zhao Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells Journal of Ginseng Research |
author_facet |
Xu De Wang Guang Yue Su Chen Zhao Fan Zhi Qu Peng Wang Yu Qing Zhao |
author_sort |
Xu De Wang |
title |
Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells |
title_short |
Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells |
title_full |
Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells |
title_fullStr |
Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells |
title_full_unstemmed |
Anticancer activity and potential mechanisms of 1C, a ginseng saponin derivative, on prostate cancer cells |
title_sort |
anticancer activity and potential mechanisms of 1c, a ginseng saponin derivative, on prostate cancer cells |
publisher |
Elsevier |
series |
Journal of Ginseng Research |
issn |
1226-8453 |
publishDate |
2018-04-01 |
description |
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/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. Keywords: 1C, AD-2, apoptosis, reactive oxygen species, Wnt/β-catenin pathway |
url |
http://www.sciencedirect.com/science/article/pii/S1226845316301154 |
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