Post-ingestion conversion of dietary indoles into anticancer agents. Issue 4 (13th August 2021)

• Record Type: Journal Article
• Authors: Lin, Li Ping; Liu, Dan; Qian, Jia Cheng; Wu, Liang; Zhao, Quan; Tan, Ren Xiang
• Is Part Of: National science review. Volume 9:Issue 4(2022)
• Publication Date: 2021-08-13
• Subjects: indole-3-carbinol -- reaction flux derailing (RFD) approach -- 2-(indol-3-ylmethyl)-3, 3′-diindolylmethane (LTr1) -- anticancer -- Lactobacillus acidophilus; Science -- Periodicals; 505
• DOI: 10.1093/nsr/nwab144
• Languages: English
• ISSNs: 2095-5138

Abstract

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. Abstract : Reaction flux derailing (RFD) approach was conceptualized, established and showcased by its application in clarifying the conversion of dietary and endogenous indoles into anticancer agents.