Glycyrrhizin ameliorates colorectal cancer progression by regulating NHEJ pathway through inhibiting HMGB1-induced DNA damage response
Abstract As one of the most common malignancies, colorectal cancer (CRC) usually starts with a benign lesion and accumulates DNA damage as it progresses to full-fledged cancer. Glycyrrhizin (GL) has been found to alleviate tumor growth and inflammation, while the role of GL influences DNA damage res...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-10-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-76155-w |
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| author | Yuhui Han Wenjiong Sheng Xiuxin Liu Haide Liu Xinyu Jia Honghui Li Changyuan Wang Bin Wang Tao Hu Yanchao Ma |
| author_facet | Yuhui Han Wenjiong Sheng Xiuxin Liu Haide Liu Xinyu Jia Honghui Li Changyuan Wang Bin Wang Tao Hu Yanchao Ma |
| author_sort | Yuhui Han |
| collection | DOAJ |
| description | Abstract As one of the most common malignancies, colorectal cancer (CRC) usually starts with a benign lesion and accumulates DNA damage as it progresses to full-fledged cancer. Glycyrrhizin (GL) has been found to alleviate tumor growth and inflammation, while the role of GL influences DNA damage response (DDR) in colorectal cancer remains unclear. GL exposure significantly reduced cell colony formation and viability with a concomitant increase in DNA fragmentation in CRC, meanwhile GL induced apoptosis by activating caspase-3. Moreover, GL induced cell cycle arrest in CRC cells at S phase, which was associated with decreased cyclin D1 in vitro. GL treatment significantly ameliorated tumor growth and promoted DDR in vivo. Mechanism analysis revealed that GL significantly downregulated the NHEJ pathway via inhibiting HMGB1. Finally, the expression of HMGB1 was abnormal regulated in CRC tissue than in adjacent normal tissues and associated with TNM stage and overall survival. Our findings indicate that HMGB1 may be a novel therapeutic target in CRC, a result that GL may serve as a promising drug for CRC treatment. |
| format | Article |
| id | doaj-art-0cf42e116e3c44ee8e9fcb2a2c823d08 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-0cf42e116e3c44ee8e9fcb2a2c823d082025-08-20T02:11:17ZengNature PortfolioScientific Reports2045-23222024-10-0114111310.1038/s41598-024-76155-wGlycyrrhizin ameliorates colorectal cancer progression by regulating NHEJ pathway through inhibiting HMGB1-induced DNA damage responseYuhui Han0Wenjiong Sheng1Xiuxin Liu2Haide Liu3Xinyu Jia4Honghui Li5Changyuan Wang6Bin Wang7Tao Hu8Yanchao Ma9Department of Immunology, Binzhou Medical UniversityDepartment of Radiotherapy, Yantaishan Hospital, Affiliated Hospital of Binzhou Medical UniversityDepartment of Immunology, Binzhou Medical UniversityDepartment of Radiotherapy, Yantaishan Hospital, Affiliated Hospital of Binzhou Medical UniversityDepartment of Immunology, Binzhou Medical UniversityDepartment of Immunology, Binzhou Medical UniversityDepartment of Immunology, Binzhou Medical UniversityDepartment of Immunology, Binzhou Medical UniversityDepartment of Immunology, Binzhou Medical UniversityDepartment of Immunology, Binzhou Medical UniversityAbstract As one of the most common malignancies, colorectal cancer (CRC) usually starts with a benign lesion and accumulates DNA damage as it progresses to full-fledged cancer. Glycyrrhizin (GL) has been found to alleviate tumor growth and inflammation, while the role of GL influences DNA damage response (DDR) in colorectal cancer remains unclear. GL exposure significantly reduced cell colony formation and viability with a concomitant increase in DNA fragmentation in CRC, meanwhile GL induced apoptosis by activating caspase-3. Moreover, GL induced cell cycle arrest in CRC cells at S phase, which was associated with decreased cyclin D1 in vitro. GL treatment significantly ameliorated tumor growth and promoted DDR in vivo. Mechanism analysis revealed that GL significantly downregulated the NHEJ pathway via inhibiting HMGB1. Finally, the expression of HMGB1 was abnormal regulated in CRC tissue than in adjacent normal tissues and associated with TNM stage and overall survival. Our findings indicate that HMGB1 may be a novel therapeutic target in CRC, a result that GL may serve as a promising drug for CRC treatment.https://doi.org/10.1038/s41598-024-76155-wColorectal cancer (CRC)Glycyrrhizin (GL)HMGB1DNA damage response (DDR)NHEJ |
| spellingShingle | Yuhui Han Wenjiong Sheng Xiuxin Liu Haide Liu Xinyu Jia Honghui Li Changyuan Wang Bin Wang Tao Hu Yanchao Ma Glycyrrhizin ameliorates colorectal cancer progression by regulating NHEJ pathway through inhibiting HMGB1-induced DNA damage response Scientific Reports Colorectal cancer (CRC) Glycyrrhizin (GL) HMGB1 DNA damage response (DDR) NHEJ |
| title | Glycyrrhizin ameliorates colorectal cancer progression by regulating NHEJ pathway through inhibiting HMGB1-induced DNA damage response |
| title_full | Glycyrrhizin ameliorates colorectal cancer progression by regulating NHEJ pathway through inhibiting HMGB1-induced DNA damage response |
| title_fullStr | Glycyrrhizin ameliorates colorectal cancer progression by regulating NHEJ pathway through inhibiting HMGB1-induced DNA damage response |
| title_full_unstemmed | Glycyrrhizin ameliorates colorectal cancer progression by regulating NHEJ pathway through inhibiting HMGB1-induced DNA damage response |
| title_short | Glycyrrhizin ameliorates colorectal cancer progression by regulating NHEJ pathway through inhibiting HMGB1-induced DNA damage response |
| title_sort | glycyrrhizin ameliorates colorectal cancer progression by regulating nhej pathway through inhibiting hmgb1 induced dna damage response |
| topic | Colorectal cancer (CRC) Glycyrrhizin (GL) HMGB1 DNA damage response (DDR) NHEJ |
| url | https://doi.org/10.1038/s41598-024-76155-w |
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