Modulation of colon cancer by nutmeg.

Abstract

Colon cancer is the most common cancer and the third leading cause of cancer mortality in humans. Using mass spectrometry-based metabolomics, the current study revealed the accumulation of four uremic toxins (cresol sulfate, cresol glucuronide, indoxyl sulfate, and phenyl sulfate) in the serum of mice harboring adenomatous polyposis coli (APC) gene mutation-induced colon cancer. These uremic toxins, likely generated from the gut microbiota, were associated with an increase in the expression of the proinflammatory cytokine IL-6 and a disorder of lipid metabolism. Nutmeg, which exhibits antimicrobial activity, attenuated the levels of uremic toxins and decreased intestinal tumorigenesis in Apc(min/+) mice. Nutmeg-treated Apc(min/+) mice had decreased IL-6 levels and normalized dysregulated lipid metabolism, suggesting that uremic toxins are responsible, in part, for the metabolic disorders that occur during tumorigenesis. These studies demonstrate a potential biochemical link among gut microbial metabolism, inflammation, and metabolic disorders and suggest that modulation of gut microbiota and lipid metabolism using dietary intervention or drugs may be effective in colon cancer chemoprevention strategies.

• Authors: Fei Li, Xiu-Wei Yang, Kristopher W Krausz, Robert G Nichols, Wei Xu, Andrew D Patterson, Frank J Gonzalez
• Journal: Journal of proteome research (J Proteome Res) Vol. 14 Issue 4 Pg. 1937-46 (Apr 03 2015) ISSN: 1535-3907 [Electronic] United States
• PMID: 25712450 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cresols
• DNA Primers
• Glucuronides
• Interleukin-6
• Plant Extracts
• Sulfuric Acid Esters
• Toxins, Biological
• uremia middle molecule toxins
• phenylsulfate
• Indican

Topics

• Adenomatous Polyposis Coli (blood, drug therapy)
• Analysis of Variance
• Animals
• Blood Chemical Analysis
• Caco-2 Cells
• Cresols (blood)
• DNA Primers (genetics)
• Gene Expression Profiling
• Glucuronides (blood)
• Humans
• Indican (blood)
• Interleukin-6 (metabolism)
• Lipid Metabolism (drug effects)
• Male
• Mass Spectrometry (methods)
• Metabolomics (methods)
• Mice
• Mice, Inbred C57BL
• Myristica (chemistry)
• Plant Extracts (analysis, pharmacology, therapeutic use)
• Sulfuric Acid Esters (blood)
• Toxins, Biological (blood, metabolism, toxicity)