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Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence
Senescence is an irreversible state of cell cycle arrest that can be triggered by multiple stimuli, such as oxygen reactive species and DNA damage. Growing evidence has proven that senescence is a tumor-suppressive approach in cancer treatment. Therefore, developing novel agents that modulate senesc...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471500/ https://www.ncbi.nlm.nih.gov/pubmed/30889805 http://dx.doi.org/10.3390/molecules24061054 |
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author | Ma, Jingxin Hu, Xiaopeng Liao, Chenghui Xiao, Haitao Zhu, Qinchang Li, Ying Liu, Zhigang Tao, Anjin He, Zhendan Xu, Chenshu Zheng, Kai |
author_facet | Ma, Jingxin Hu, Xiaopeng Liao, Chenghui Xiao, Haitao Zhu, Qinchang Li, Ying Liu, Zhigang Tao, Anjin He, Zhendan Xu, Chenshu Zheng, Kai |
author_sort | Ma, Jingxin |
collection | PubMed |
description | Senescence is an irreversible state of cell cycle arrest that can be triggered by multiple stimuli, such as oxygen reactive species and DNA damage. Growing evidence has proven that senescence is a tumor-suppressive approach in cancer treatment. Therefore, developing novel agents that modulate senescence may be an alternative strategy against cancer. In our study, we investigated the inhibitory effect of gypenoside L (Gyp-L), a saponin isolated from Gynostemma pentaphyllum, on cancer cell growth. We found that Gyp-L increased the SA-β-galactosidase activity, promoted the production of senescence-associated secretory cytokines, and inhibited cell proliferation of human liver and esophageal cancer cells. Moreover, Gyp-L caused cell cycle arrest at S phase, and activated senescence-related cell cycle inhibitor proteins (p21 and p27) and their upstream regulators. In addition, Gyp-L activated p38 and ERK MAPK pathways and NF-κB pathway to induce senescence. Consistently, adding chemical inhibitors efficiently counteracted the Gyp-L-mediated senescence, growth inhibition, and cell cycle arrest in cancer cells. Furthermore, treatment with Gyp-L, enhanced the cytotoxicity of clinic therapeutic drugs, including 5-fluorouracil and cisplatin, on cancer cells. Overall, these results indicate that Gyp-L inhibits proliferation of cancer cells by inducing senescence and renders cancer cells more sensitive to chemotherapy. |
format | Online Article Text |
id | pubmed-6471500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64715002019-04-26 Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence Ma, Jingxin Hu, Xiaopeng Liao, Chenghui Xiao, Haitao Zhu, Qinchang Li, Ying Liu, Zhigang Tao, Anjin He, Zhendan Xu, Chenshu Zheng, Kai Molecules Article Senescence is an irreversible state of cell cycle arrest that can be triggered by multiple stimuli, such as oxygen reactive species and DNA damage. Growing evidence has proven that senescence is a tumor-suppressive approach in cancer treatment. Therefore, developing novel agents that modulate senescence may be an alternative strategy against cancer. In our study, we investigated the inhibitory effect of gypenoside L (Gyp-L), a saponin isolated from Gynostemma pentaphyllum, on cancer cell growth. We found that Gyp-L increased the SA-β-galactosidase activity, promoted the production of senescence-associated secretory cytokines, and inhibited cell proliferation of human liver and esophageal cancer cells. Moreover, Gyp-L caused cell cycle arrest at S phase, and activated senescence-related cell cycle inhibitor proteins (p21 and p27) and their upstream regulators. In addition, Gyp-L activated p38 and ERK MAPK pathways and NF-κB pathway to induce senescence. Consistently, adding chemical inhibitors efficiently counteracted the Gyp-L-mediated senescence, growth inhibition, and cell cycle arrest in cancer cells. Furthermore, treatment with Gyp-L, enhanced the cytotoxicity of clinic therapeutic drugs, including 5-fluorouracil and cisplatin, on cancer cells. Overall, these results indicate that Gyp-L inhibits proliferation of cancer cells by inducing senescence and renders cancer cells more sensitive to chemotherapy. MDPI 2019-03-18 /pmc/articles/PMC6471500/ /pubmed/30889805 http://dx.doi.org/10.3390/molecules24061054 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ma, Jingxin Hu, Xiaopeng Liao, Chenghui Xiao, Haitao Zhu, Qinchang Li, Ying Liu, Zhigang Tao, Anjin He, Zhendan Xu, Chenshu Zheng, Kai Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence |
title | Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence |
title_full | Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence |
title_fullStr | Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence |
title_full_unstemmed | Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence |
title_short | Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence |
title_sort | gypenoside l inhibits proliferation of liver and esophageal cancer cells by inducing senescence |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471500/ https://www.ncbi.nlm.nih.gov/pubmed/30889805 http://dx.doi.org/10.3390/molecules24061054 |
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