Back to Search
Start Over
Post-ingestion conversion of dietary indoles into anticancer agents
- Source :
- National science review. 9(4)
- Publication Year :
- 2020
-
Abstract
- There are health benefits from consuming cruciferous vegetables that release indole-3-carbinol (I3C), but the in vivo transformation of I3C-related indoles remains underinvestigated. Here we detail the post-ingestion conversion of I3C into antitumor agents, 2-(indol-3-ylmethyl)-3,3′-diindolylmethane (LTr1) and 3,3′-diindolylmethane (DIM), by conceptualizing and materializing the reaction flux derailing (RFD) approach as a means of unraveling these stepwise transformations to be non-enzymatic but pH-dependent and gut microbe-sensitive. In the upper (or acidic) gastrointestinal tract, LTr1 is generated through Michael addition of 3-methyleneindolium (3MI, derived in situ from I3C) to DIM produced from I3C via the formaldehyde-releasing (major) and CO2-liberating (minor) pathways. In the large intestine, ‘endogenous’ I3C and DIM can form, respectively, from couplings of formaldehyde with one and two molecules of indole (a tryptophan catabolite). Acid-producing gut bacteria such as Lactobacillus acidophilus facilitate the H+-promotable steps. This work updates our understanding of the merits of I3C consumption and identifies LTr1 as a drug candidate.
- Subjects :
- Multidisciplinary
business.industry
Medicine
Ingestion
Pharmacology
business
Subjects
Details
- ISSN :
- 2053714X
- Volume :
- 9
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- National science review
- Accession number :
- edsair.doi.dedup.....226d029b78daf94dca84983268a65af2