Glycyrrhizin ameliorates colorectal cancer progression by regulating NHEJ pathway through inhibiting HMGB1-induced DNA damage response.
HMGB1 Protein
/ metabolism
Glycyrrhizic Acid
/ pharmacology
Colorectal Neoplasms
/ drug therapy
Humans
DNA Damage
/ drug effects
Animals
Cell Line, Tumor
Male
Mice
Apoptosis
/ drug effects
Female
Disease Progression
Xenograft Model Antitumor Assays
Cell Proliferation
/ drug effects
Cell Cycle Checkpoints
/ drug effects
Colorectal cancer (CRC)
DNA damage response (DDR)
Glycyrrhizin (GL)
HMGB1
NHEJ
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 10 2024
23 10 2024
Historique:
received:
08
06
2024
accepted:
10
10
2024
medline:
23
10
2024
pubmed:
23
10
2024
entrez:
22
10
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39438689
doi: 10.1038/s41598-024-76155-w
pii: 10.1038/s41598-024-76155-w
doi:
Substances chimiques
HMGB1 Protein
0
Glycyrrhizic Acid
6FO62043WK
HMGB1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
24948Subventions
Organisme : Medical and Health Science and Technology Project of Shandong Province
ID : 202309030619
Organisme : National Natural Science Foundation of China
ID : 82203543
Organisme : Initial project of Binzhou Medical University
ID : 50012304458
Organisme : Shandong Province Natural Science Foundation
ID : ZR2022QH267
Informations de copyright
© 2024. The Author(s).
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