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Biochem Biophys Res Commun. 2018 Feb 5;496(2):316-323. doi: 10.1016/j.bbrc.2017.12.171. Epub 2018 Jan 3.

RvD1 inhibits TNFα-induced c-Myc expression in normal intestinal epithelial cells and destabilizes hyper-expressed c-Myc in colon cancer cells.

Author information

1
Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
2
Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: surh@snu.ac.kr.

Abstract

Inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, are persistent disorders that lead to development of colitis-associated cancer (CAC). Facilitated resolution of colitis has been addressed as a novel therapeutic strategy to control development of CAC. Resolvin D1 (RvD1) is an endogenous lipid mediator that is generated from docosahexaenoic acid during the resolution of inflammation. Although the pro-resolving effects of RvDs have been extensively investigated and well defined, the role for RvD1 in CAC remains largely unknown. In this study, we found that RvD1 inhibited the expression of c-Myc in normal colon cells stimulated with tumor necrosis factor-α (TNFα) and also in colon cancer cells. The suppression of TNFα-induced upregulation of c-Myc in normal cells was mediated through attenuation of NF-κB signaling. Notably, RvD1 destabilized the constitutively overexpressed c-Myc protein in HCT 116 human colon cancer cells by stimulating its ubiquitination and subsequent proteasomal degradation. Further, we revealed that RvD1 stimulated c-Myc degradation through direct interaction with the ALX/FPR2 receptor. This interaction resulted in inhibition of activation of extracellular signal-regulated kinase, thereby attenuating phosphorylation-dependent stabilization of c-Myc.

KEYWORDS:

Colitis-associated cancer; Colon cancer; Resolution of inflammation; Resolvin D1; c-Myc

PMID:
29305860
DOI:
10.1016/j.bbrc.2017.12.171
[Indexed for MEDLINE]

Publication type, MeSH terms, Substances

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