Electrophilic reactive aldehydes as a therapeutic target in colorectal cancer prevention and treatment.

Autor: Gobert AP; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA., Asim M; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Smith TM; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Williams KJ; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Barry DP; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Allaman MM; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., McNamara KM; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA., Hawkins CV; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Delgado AG; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Zhao S; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Piazuelo MB; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA., Washington MK; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Coburn LA; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA.; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA.; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA., Rathmacher JA; MTI BioTech Inc., Iowa State University Research Park, Ames, IA, USA.; Department of Animal Science, Iowa State University, Ames, IA, USA., Wilson KT; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. keith.wilson@vumc.org.; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA. keith.wilson@vumc.org.; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA. keith.wilson@vumc.org.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. keith.wilson@vumc.org.; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA. keith.wilson@vumc.org.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2023 May; Vol. 42 (20), pp. 1685-1691. Date of Electronic Publication: 2023 Apr 10.
DOI: 10.1038/s41388-023-02691-w
Abstrakt: Colorectal cancer (CRC) is a major health problem worldwide. Dicarbonyl electrophiles, such as isolevuglandins (isoLGs), are generated from lipid peroxidation and form covalent adducts with amine-containing macromolecules. We have shown high levels of adducts of isoLGs in colonic epithelial cells of patients with CRC. We thus investigated the role of these reactive aldehydes in colorectal cancer development. We found that 2-hydroxybenzylamine (2-HOBA), a natural compound derived from buckwheat seeds that acts as a potent scavenger of electrophiles, is bioavailable in the colon of mice after supplementation in the drinking water and does not affect the colonic microbiome. 2-HOBA reduced the level of isoLG adducts to lysine as well as tumorigenesis in models of colitis-associated carcinogenesis and of sporadic CRC driven by specific deletion of the adenomatous polyposis coli gene in colonic epithelial cells. In parallel, we found that oncogenic NRF2 activation and signaling were decreased in the colon of 2-HOBA-treated mice. Additionally, the growth of xenografted human HCT116 CRC cells in nude mice was significantly attenuated by 2-HOBA supplementation. In conclusion, 2-HOBA represents a promising natural compound for the prevention and treatment of CRC.
(© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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