Suppression of C-C chemokine receptor 1 is a key regulation for colon cancer chemoprevention in AOM/DSS mice by fucoxanthin.

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(Ser473) (0.2-fold in mucosal crypts), Cyclin D1 (0.4-fold in mucosal crypts), and pSmad2(Ser465/467) (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.

• Authors: Masaru Terasaki, Shion Ono, Saki Hashimoto, Atsuhito Kubota, Hiroyuki Kojima, Tohru Ohta, Takuji Tanaka, Hayato Maeda, Kazuo Miyashita, Michihiro Mutoh
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 99 Pg. 108871 (01 2022) ISSN: 1873-4847 [Electronic] United States
• PMID: 34571188 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Chemokines, CC
• Receptors, CCR1
• Smad2 Protein
• Xanthophylls
• fucoxanthin
• Cyclin D1
• Dextran Sulfate
• Proto-Oncogene Proteins c-akt
• Azoxymethane

Topics

• Animals
• Azoxymethane (adverse effects)
• Chemokines, CC (metabolism)
• Colonic Neoplasms (chemically induced, genetics, metabolism, prevention & control)
• Cyclin D1 (genetics, metabolism)
• Dextran Sulfate (adverse effects)
• Disease Models, Animal
• Humans
• Male
• Mice
• Mice, Inbred ICR
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Receptors, CCR1 (genetics, metabolism)
• Smad2 Protein (genetics, metabolism)
• Xanthophylls (administration & dosage)