Post-ingestion conversion of dietary indoles into anticancer agents  

作　　者：Li Ping Lin Dan Liu Jia Cheng Qian Liang Wu Quan Zhao Ren Xiang Tan 

机构地区：[1]State Key Laboratory of Pharmaceutical Biotechnology,Institute of Functional Biomolecules,Nanjing University,Nanjing 210023,China [2]State Key Laboratory Cultivation Base for TCM Quality and Efficacy,Nanjing University of Chinese Medicine,Nanjing 210023,China

出　　处：《National Science Review》2022年第4期123-133,共11页国家科学评论（英文版）

基　　金：supported by the National Natural Science Foundation of China (81991524 and 82073721);the National Key Research and Development Program of China(2018YFC1706200);the Jiangsu Provincial Natural Science Foundation (BK20180159)。

摘　　要：There are health benefits from consuming cruciferous vegetables that release indole-3-carbinol(I3 C), but the in vivo transformation of I3 C-related indoles remains underinvestigated. Here we detail the post-ingestion conversion of I3 C 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 p H-dependent and gut microbe-sensitive. In the upper(or acidic) gastrointestinal tract, LTr1 is generated through Michael addition of 3-methyleneindolium(3 MI, derived in situ from I3 C) to DIM produced from I3 C via the formaldehyde-releasing(major) and CO_(2)-liberating(minor) pathways. In the large intestine,‘endogenous' I3 C 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 I3 C consumption and identifies LTr1 as a drug candidate.

关 键 词：INDOLE-3-CARBINOL reaction flux derailing(RFD)approach 2-(indol-3-ylmethyl)-3 3′-diindolylmethane(LTr1) ANTICANCER Lactobacillus acidophilus 

分 类 号：R284[医药卫生—中药学]