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Oridonin Dose-Dependently Modulates the Cell Senescence and Apoptosis of Gastric Cancer Cells

Gastric cancer (GC) is the fourth most lethal cancer. Effective treatments are lacking, and our knowledge of the pathogenic mechanisms in play is poor. Oridonin from the Chinese herb Rabdosia rubescens exerts various anticancer activities. However, the dose-dependent effects of oridonin on human GC...

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Autores principales: Wang, Yiping, Lv, Hang, Dai, Chunyan, Wang, Xi, Yin, Yifei, Chen, Zhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595004/
https://www.ncbi.nlm.nih.gov/pubmed/34795783
http://dx.doi.org/10.1155/2021/5023536
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author Wang, Yiping
Lv, Hang
Dai, Chunyan
Wang, Xi
Yin, Yifei
Chen, Zhe
author_facet Wang, Yiping
Lv, Hang
Dai, Chunyan
Wang, Xi
Yin, Yifei
Chen, Zhe
author_sort Wang, Yiping
collection PubMed
description Gastric cancer (GC) is the fourth most lethal cancer. Effective treatments are lacking, and our knowledge of the pathogenic mechanisms in play is poor. Oridonin from the Chinese herb Rabdosia rubescens exerts various anticancer activities. However, the dose-dependent effects of oridonin on human GC remain unclear. Here, we found that oridonin inhibited GC cell growth in a time- and dose-dependent manner. Low-dose oridonin induced GC cell cycle arrest at G0/G1 and cell senescence by suppressing the c-Myc-AP4 pathway and enhancing p53-p21 signaling. AP4 overexpression partly abrogated the oridonin-induced senescence of GC cells. High-dose oridonin induced apoptosis and autophagy, with the autophagy inhibitor BafA1 attenuating oridonin-induced apoptosis. Together, the findings indicate that oridonin at different doses modulates GC cell senescence and apoptosis; oridonin may thus usefully treat GC.
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spelling pubmed-85950042021-11-17 Oridonin Dose-Dependently Modulates the Cell Senescence and Apoptosis of Gastric Cancer Cells Wang, Yiping Lv, Hang Dai, Chunyan Wang, Xi Yin, Yifei Chen, Zhe Evid Based Complement Alternat Med Research Article Gastric cancer (GC) is the fourth most lethal cancer. Effective treatments are lacking, and our knowledge of the pathogenic mechanisms in play is poor. Oridonin from the Chinese herb Rabdosia rubescens exerts various anticancer activities. However, the dose-dependent effects of oridonin on human GC remain unclear. Here, we found that oridonin inhibited GC cell growth in a time- and dose-dependent manner. Low-dose oridonin induced GC cell cycle arrest at G0/G1 and cell senescence by suppressing the c-Myc-AP4 pathway and enhancing p53-p21 signaling. AP4 overexpression partly abrogated the oridonin-induced senescence of GC cells. High-dose oridonin induced apoptosis and autophagy, with the autophagy inhibitor BafA1 attenuating oridonin-induced apoptosis. Together, the findings indicate that oridonin at different doses modulates GC cell senescence and apoptosis; oridonin may thus usefully treat GC. Hindawi 2021-11-09 /pmc/articles/PMC8595004/ /pubmed/34795783 http://dx.doi.org/10.1155/2021/5023536 Text en Copyright © 2021 Yiping Wang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Yiping
Lv, Hang
Dai, Chunyan
Wang, Xi
Yin, Yifei
Chen, Zhe
Oridonin Dose-Dependently Modulates the Cell Senescence and Apoptosis of Gastric Cancer Cells
title Oridonin Dose-Dependently Modulates the Cell Senescence and Apoptosis of Gastric Cancer Cells
title_full Oridonin Dose-Dependently Modulates the Cell Senescence and Apoptosis of Gastric Cancer Cells
title_fullStr Oridonin Dose-Dependently Modulates the Cell Senescence and Apoptosis of Gastric Cancer Cells
title_full_unstemmed Oridonin Dose-Dependently Modulates the Cell Senescence and Apoptosis of Gastric Cancer Cells
title_short Oridonin Dose-Dependently Modulates the Cell Senescence and Apoptosis of Gastric Cancer Cells
title_sort oridonin dose-dependently modulates the cell senescence and apoptosis of gastric cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595004/
https://www.ncbi.nlm.nih.gov/pubmed/34795783
http://dx.doi.org/10.1155/2021/5023536
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