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DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis

Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan (CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly...

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Autores principales: Wang, Yuanyuan, Wei, Bin, Wang, Danping, Wu, Jingjing, Gao, Jianhua, Zhong, Haiqing, Sun, Yang, Xu, Qiang, Liu, Wen, Gu, Yanhong, Guo, Wenjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799857/
https://www.ncbi.nlm.nih.gov/pubmed/35127384
http://dx.doi.org/10.1016/j.apsb.2021.03.043
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author Wang, Yuanyuan
Wei, Bin
Wang, Danping
Wu, Jingjing
Gao, Jianhua
Zhong, Haiqing
Sun, Yang
Xu, Qiang
Liu, Wen
Gu, Yanhong
Guo, Wenjie
author_facet Wang, Yuanyuan
Wei, Bin
Wang, Danping
Wu, Jingjing
Gao, Jianhua
Zhong, Haiqing
Sun, Yang
Xu, Qiang
Liu, Wen
Gu, Yanhong
Guo, Wenjie
author_sort Wang, Yuanyuan
collection PubMed
description Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan (CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA (dsDNA) from the intestine, leading to cyclic-GMP-AMP synthase (cGAS)‒stimulator of interferon genes (STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination (HR) repair and downregulate dsDNA‒cGAS‒STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.
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spelling pubmed-87998572022-02-03 DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis Wang, Yuanyuan Wei, Bin Wang, Danping Wu, Jingjing Gao, Jianhua Zhong, Haiqing Sun, Yang Xu, Qiang Liu, Wen Gu, Yanhong Guo, Wenjie Acta Pharm Sin B Original Article Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan (CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA (dsDNA) from the intestine, leading to cyclic-GMP-AMP synthase (cGAS)‒stimulator of interferon genes (STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination (HR) repair and downregulate dsDNA‒cGAS‒STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11. Elsevier 2022-01 2021-04-29 /pmc/articles/PMC8799857/ /pubmed/35127384 http://dx.doi.org/10.1016/j.apsb.2021.03.043 Text en © 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Wang, Yuanyuan
Wei, Bin
Wang, Danping
Wu, Jingjing
Gao, Jianhua
Zhong, Haiqing
Sun, Yang
Xu, Qiang
Liu, Wen
Gu, Yanhong
Guo, Wenjie
DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis
title DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis
title_full DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis
title_fullStr DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis
title_full_unstemmed DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis
title_short DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis
title_sort dna damage repair promotion in colonic epithelial cells by andrographolide downregulated cgas‒sting pathway activation and contributed to the relief of cpt-11-induced intestinal mucositis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799857/
https://www.ncbi.nlm.nih.gov/pubmed/35127384
http://dx.doi.org/10.1016/j.apsb.2021.03.043
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