结直肠癌
癌变
癌症研究
家族性腺瘤性息肉病
生物
电泳剂
偶氮甲烷
致癌物
癌症
癌症预防
结肠炎
免疫学
生物化学
药理学
基因
遗传学
催化作用
作者
Alain P. Gobert,Mohammad Asim,Thaddeus M. Smith,Kamery J. Williams,Daniel P. Barry,Margaret M. Allaman,Kara M. McNamara,Caroline V. Hawkins,Alberto Delgado,Shilin Zhao,M. Blanca Piazuelo,M. Kay Washington,Lori A. Coburn,John A. Rathmacher,Keith T. Wilson
出处
期刊:Oncogene
[Springer Nature]
日期:2023-04-10
卷期号:42 (20): 1685-1691
被引量:1
标识
DOI:10.1038/s41388-023-02691-w
摘要
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.
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