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Post-ingestion conversion of dietary indoles into anticancer agents.

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.

SUBMITTER: Lin LP

PROVIDER: S-EPMC9053945 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Post-ingestion conversion of dietary indoles into anticancer agents.

Lin Li Ping LP Liu Dan D Qian Jia Cheng JC Wu Liang L Zhao Quan Q Tan Ren Xiang RX

National science review 20210813 4

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 transforma ...[more]

PMID: 35505660

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Post-ingestion conversion of dietary indoles into anticancer agents.

Publications

Post-ingestion conversion of dietary indoles into anticancer agents.

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