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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...

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Autores principales: Ma, Jingxin, Hu, Xiaopeng, Liao, Chenghui, Xiao, Haitao, Zhu, Qinchang, Li, Ying, Liu, Zhigang, Tao, Anjin, He, Zhendan, Xu, Chenshu, Zheng, Kai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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