Bidirectional effects of the tryptophan metabolite indole-3-acetaldehyde on colorectal cancer  

作　　者：Ze Dai Kai-Li Deng Xiao-Mei Wang Dong-Xue Yang Chun-Lan Tang Yu-Ping Zhou 

机构地区：[1]Department of Gastroenterology,The First Affiliated Hospital of Ningbo University,Ningbo 315020,Zhejiang Province,China [2]Health Science Center,Ningbo University,Ningbo 315211,Zhejiang Province,China [3]School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,Guangdong Province,China [4]Institute of Digestive Disease of Ningbo University,Ningbo University,Ningbo 315020,Zhejiang Province,China [5]Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology,Ningbo Key Laboratory,Ningbo 315020,Zhejiang Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第6期2697-2715,共19页世界胃肠肿瘤学杂志（英文版）（电子版）

基　　金：Supported by Zhejiang Provincial Natural Science Foundation of China,No.LTGD23C040008,No.LBY23H200006,and No.LQ22H030004.

摘　　要：BACKGROUND Colorectal cancer(CRC)has a high incidence and mortality.Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis,progression,and metastasis of CRC.AIM To investigate the effect of indole-3-acetaldehyde(IAAD)on CRC.METHODS The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines(HCT116 and DLD-1).Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests.Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide.Invasiveness was investigated using the transwell assay.Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor(AhR)downstream genes.The PharmMapper,SEA,and SWISS databases were used to screen for potential target proteins of IAAD,and the core proteins were identified through the String database.RESULTS IAAD reduced tumorigenesis in a syngeneic mouse model.In CRC cell lines HCT116 and DLD1,IAAD exhibited cytotoxicity starting at 24 h of treatment,while it reduced Ki67 expression in the nucleus.The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells,which may be related to the activation of AhR.IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells.At low concentrations(<12.5μmol/L),IAAD only exhibited cytotoxic effects without promoting cell invasion.In addition,predictions based on online databases,protein-protein interaction analysis,and molecular docking showed that IAAD can bind to matrix metalloproteinase-9(MMP9),angiotensin converting enzyme(ACE),poly(ADP-ribose)polymerase-1(PARP1),matrix metalloproteinase-2(MMP2),and myeloperoxidase(MPO).CONCLUSION Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC;howe

关 键 词：Indole-3-acetaldehyde Colorectal cancer Tryptophan metabolism Apoptosis Epithelial-mesenchymal transition 

分 类 号：R735.34[医药卫生—肿瘤]