Back to Search
Start Over
Suppression of C-C chemokine receptor 1 is a key regulation for colon cancer chemoprevention in AOM/DSS mice by fucoxanthin.
- Source :
-
The Journal of nutritional biochemistry [J Nutr Biochem] 2022 Jan; Vol. 99, pp. 108871. Date of Electronic Publication: 2021 Sep 24. - Publication Year :
- 2022
-
Abstract
- Fucoxanthin (Fx) has shown potential cancer chemopreventive functions in a carcinogenic murine azoxymethane/dextran sodium sulfate (AOM/DSS) model. However, the molecular mechanisms based on transcriptome profiles in vivo remain poorly understood. We investigated Fx-dependent alterations of the transcriptome with cancer-associated proteins in colorectal mucosal tissue obtained from AOM/DSS mice with or without Fx treatment. Fx administration (50 mg/kg body weight for 14 weeks) significantly prevented the onset of colorectal adenocarcinoma in AOM/DSS mice. A transcriptome analysis revealed that 11 signals, including adhesion, cell cycle, chemokine receptor, interleukin, MAPK, PI3K/AKT, p53, RAS, STAT, TGF-β, and Wnt were remarkably altered by Fx administration. In particular, chemokine (C-C motif) receptor 1 (Ccr1), which is contained in a gene set related to cytokine-cytokine receptor interactions, was the only significantly down-regulated gene after Fx administration for both 7 and 14 weeks. CCR1, AKT, Cyclin D1, and Smad2 were found to play central roles in the 11 signals shown above. Fx administration significantly down-regulated CCR1 (0.3- and 0.5-fold in mucosal crypts and lamina propria, respectively), pAKT(Ser <superscript>473</superscript> ) (0.2-fold in mucosal crypts), Cyclin D1 (0.4-fold in mucosal crypts), and pSmad2(Ser <superscript>465/467</superscript> ) (0.7-fold in mucosal crypts) compared with proteins in these tissues of control mice after Fx administration for 14 weeks. Our findings suggested that Fx exerts a chemopreventive effect in AOM/DSS mice through attenuation of CCR1 expression along with 11 cancer-associated signals.<br /> (Copyright © 2021. Published by Elsevier Inc.)
- Subjects :
- Animals
Azoxymethane adverse effects
Chemokines, CC metabolism
Colonic Neoplasms chemically induced
Colonic Neoplasms genetics
Cyclin D1 genetics
Cyclin D1 metabolism
Dextran Sulfate adverse effects
Disease Models, Animal
Humans
Male
Mice
Mice, Inbred ICR
Proto-Oncogene Proteins c-akt genetics
Proto-Oncogene Proteins c-akt metabolism
Receptors, CCR1 metabolism
Smad2 Protein genetics
Smad2 Protein metabolism
Colonic Neoplasms metabolism
Colonic Neoplasms prevention & control
Receptors, CCR1 genetics
Xanthophylls administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4847
- Volume :
- 99
- Database :
- MEDLINE
- Journal :
- The Journal of nutritional biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 34571188
- Full Text :
- https://doi.org/10.1016/j.jnutbio.2021.108871