ReferenceID 6155
Rosmarinic acid represses colitis-associated colon cancer: A pivotal involvement of the TLR4-mediated NF-κB-STAT3 axis
Neoplasia
Previously, we found that rosmarinic acid (RA) exerted anti-inflammatory activities in a dextran sulfate sodium (DSS)-induced colitis model. Here, we investigated the anti-tumor effects of RA on colitis-associated colon
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Record Fields
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- Reference Id
- 6155
- Evidence Id
- 22745
- Core Evidence Id
- 22745
- Source Reference Id
- 5574
- Herb2 Reference Id
- HBREF006371
- Subject Paper Key
- HBIN042438_34077834
- Pubmed Id
- 34077834
- Doi
- 10.1016/j.neo.2021.05.002
- Paper Title
- Rosmarinic acid represses colitis-associated colon cancer: A pivotal involvement of the TLR4-mediated NF-κB-STAT3 axis
- Paper Abstract
- Previously, we found that rosmarinic acid (RA) exerted anti-inflammatory activities in a dextran sulfate sodium (DSS)-induced colitis model. Here, we investigated the anti-tumor effects of RA on colitis-associated colon cancer (CAC) and the underlying molecular mechanisms. We established an azoxymethane (AOM)/DSS-induced CAC murine model for in vivo studies and used a conditioned media (CM) culture system in vitro. H&E staining, immunohistochemistry, western blot assay, enzyme-linked immunosorbent assay, molecular docking, co-immunoprecipitation, and immunofluorescence assay were utilized to investigate how RA prevented colorectal cancer. In the AOM/DSS-induced CAC murine model, RA significantly reduced colitis severity, inflammation-related protein expression, tumor incidence, and colorectal adenoma development. It significantly modulated toll-like receptor-4 (TLR4)-mediated nuclear factor-kappa B (NF-kappaB) and signal transducer and activator of transcription 3 (STAT3) activation, thus attenuating the expression of anti-apoptotic factors, which mediate transcription factor-dependent tumor growth. In vitro, RA inhibited CM-induced TLR4 overexpression and competitively inhibited TLR4-myeloid differentiation factor 2 complex in an inflammatory microenvironment. Thus, RA suppressed NF-kappaB and STAT3 activation in colon cancer cells in an inflammatory microenvironment. Therefore, RA suppressed colitis-associated tumorigenesis in the AOM/DSS-induced CAC murine model and abrogated human colon cancer progression in an inflammatory microenvironment by propitiating TLR4-mediated NF-kappaB and STAT3 activation, pleiotropically.
- Journal
- Neoplasia
- Publish Year
- 2021
- Experiment Subject
- mouse; human; cac murine model
- Experiment Type
- Animal Experiment
- Phenotype Related
- Colon Cancer; Tumor; Colorectal Cancer; Colorectal Adenoma; Colitis; Colitis-associated Colon Cancer
- Paper Title Cn
- Paper Title En
- Rosmarinic acid represses colitis-associated colon cancer: A pivotal involvement of the TLR4-mediated NF-κB-STAT3 axis
- Bilingual Status
- semi_complete