Electrophilic reactive aldehydes as a therapeutic target in colorectal cancer prevention and treatment.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
07
02
2023
accepted:
29
03
2023
revised:
28
03
2023
medline:
15
5
2023
pubmed:
11
4
2023
entrez:
10
4
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37037901
doi: 10.1038/s41388-023-02691-w
pii: 10.1038/s41388-023-02691-w
pmc: PMC10182918
mid: NIHMS1892542
doi:
Substances chimiques
Aldehydes
0
2-(aminomethyl)phenol
932-30-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1685-1691Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK128200
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK058404
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA086862
Pays : United States
Organisme : NCI NIH HHS
ID : R41 CA257262
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA116087
Pays : United States
Organisme : BLRD VA
ID : I01 BX004366
Pays : United States
Organisme : CSRD VA
ID : I01 CX002171
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009592
Pays : United States
Informations de copyright
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
Références
Front Immunol. 2022 Jan 07;12:807648
pubmed: 35069592
Biomed Pharmacother. 2023 Feb;158:114092
pubmed: 36493697
CA Cancer J Clin. 2021 May;71(3):209-249
pubmed: 33538338
Gut. 2001 Apr;48(4):526-35
pubmed: 11247898
Regul Toxicol Pharmacol. 2018 Nov;99:225-232
pubmed: 30266239
Mol Cell. 2002 May;9(5):1031-44
pubmed: 12049739
Cell. 1990 Jun 1;61(5):759-67
pubmed: 2188735
Am J Physiol Gastrointest Liver Physiol. 2022 Jan 1;322(1):G169-G182
pubmed: 34878937
Pulm Circ. 2017 Feb 1;7(1):186-199
pubmed: 28680578
World J Gastroenterol. 2005 Jan 21;11(3):403-6
pubmed: 15637754
Science. 1998 Sep 4;281(5382):1509-12
pubmed: 9727977
Redox Biol. 2021 Jun;42:101880
pubmed: 33541845
Free Radic Biol Med. 2007 Nov 15;43(10):1388-93
pubmed: 17936185
BMC Pharmacol Toxicol. 2020 Jan 6;21(1):3
pubmed: 31907026
Biochemistry. 2009 Nov 17;48(45):10775-81
pubmed: 19824699
J Alzheimers Dis. 2011;27(1):49-59
pubmed: 21709376
Regul Toxicol Pharmacol. 2018 Dec;100:52-58
pubmed: 30359704
BMC Pharmacol Toxicol. 2019 Jan 05;20(1):1
pubmed: 30611293
Am J Clin Nutr. 1993 May;57(5 Suppl):779S-785S; discussion 785S-786S
pubmed: 8475896
Biochemistry. 2014 Apr 22;53(15):2436-41
pubmed: 24684440
PLoS One. 2020 Oct 28;15(10):e0239601
pubmed: 33112876
Regul Toxicol Pharmacol. 2018 Oct;98:190-198
pubmed: 30075181
Annu Rev Pharmacol Toxicol. 2013;53:401-26
pubmed: 23294312
Int J Cancer. 2008 Nov 15;123(10):2460-4
pubmed: 18729200
Gastroenterology. 2021 Mar;160(4):1256-1268.e9
pubmed: 33189701
Colorectal Dis. 2011 Oct;13(10):1085-99
pubmed: 20412095
JAMA Surg. 2015 Jan;150(1):17-22
pubmed: 25372703
Nat Commun. 2020 Aug 14;11(1):4084
pubmed: 32796843
Pharmaceutics. 2010 Mar;2(1):18-29
pubmed: 21822464
Science. 2005 Dec 2;310(5753):1504-10
pubmed: 16293724
J Inflamm (Lond). 2010 Feb 01;7:7
pubmed: 20181058
Biochemistry. 1999 Jul 20;38(29):9389-96
pubmed: 10413514
Pharmacol Ther. 2020 Jan;205:107418
pubmed: 31629006
J Clin Invest. 2016 Jan;126(1):50-67
pubmed: 26595812
Life Sci. 2019 Dec 1;238:116968
pubmed: 31628914
J Cancer Prev. 2021 Mar 30;26(1):41-53
pubmed: 33842405
Biomolecules. 2020 Sep 25;10(10):
pubmed: 32992842
Cancer Res. 2009 Apr 15;69(8):3382-9
pubmed: 19336570