title: 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.affiliation: †Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.|‡Research Center for Differentiation and Development of Basic Theory of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: §State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Xiu-Wei
authors.initials: XW
authors.lastname: Yang
authors.affiliation: †Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors.forename: Kristopher W
authors.initials: KW
authors.lastname: Krausz
authors.affiliation: ∥Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nichols
authors.affiliation: §State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: ∥Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Patterson
authors.affiliation: †Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000097:blood* / Q000188:drug therapy*; D000704:Analysis of Variance; D000818:Animals; D001774:Blood Chemical Analysis; D018938:Caco-2 Cells; D003408:Cresols / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D020719:Glucuronides / Q000097:blood; D006801:Humans; D007200:Indican / Q000097:blood; D015850:Interleukin-6 / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D026323:Myristica / Q000737:chemistry*; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D013463:Sulfuric Acid Esters / Q000097:blood; D014118:Toxins, Biological / Q000097:blood* / Q000378:metabolism* / Q000633:toxicity
chemical_list: D003408:Cresols; D017931:DNA Primers; D020719:Glucuronides; D015850:Interleukin-6; D010936:Plant Extracts; D013463:Sulfuric Acid Esters; D014118:Toxins, Biological; C026865:uremia middle molecule toxins; C025208:phenylsulfate; D007200:Indican
keywords: Colon cancer; inflammation; mass spectrometry; metabolomics; nutmeg; uremic toxin