دورية أكاديمية
Bidirectional effects of the tryptophan metabolite indole-3-acetaldehyde on colorectal cancer.
| العنوان: | Bidirectional effects of the tryptophan metabolite indole-3-acetaldehyde on colorectal cancer. |
|---|---|
| المؤلفون: | Dai Z; Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China.; Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China., Deng KL; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, Guangdong Province, China., Wang XM; Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China.; Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China., Yang DX; Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China.; Institute of Digestive Disease of Ningbo University, Ningbo University, Ningbo 315020, Zhejiang Province, China.; Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology, Ningbo Key Laboratory, Ningbo 315020, Zhejiang Province, China., Tang CL; Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China., Zhou YP; Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China.; Institute of Digestive Disease of Ningbo University, Ningbo University, Ningbo 315020, Zhejiang Province, China.; Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology, Ningbo Key Laboratory, Ningbo 315020, Zhejiang Province, China. fyzhouyuping@nbu.edu.cn. |
| المصدر: | World journal of gastrointestinal oncology [World J Gastrointest Oncol] 2024 Jun 15; Vol. 16 (6), pp. 2697-2715. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Baishideng Publishing Group Country of Publication: China NLM ID: 101532470 Publication Model: Print Cited Medium: Print ISSN: 1948-5204 (Print) NLM ISO Abbreviation: World J Gastrointest Oncol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Publication: 2014- : Pleasanton, CA : Baishideng Publishing Group Original Publication: Beijing, China : Baishideng |
| مستخلص: | 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 (< 12.5 μmol/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; however, at high concentrations (≥ 25 μmol/L), it can also promote epithelial-mesenchymal transition and invasion in CRC cells. IAAD activates AhR and directly binds MMP9, ACE, PARP1, MMP2, and MPO, which partly reveals why it has a bidirectional effect. Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose. (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.) |
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| فهرسة مساهمة: | Keywords: Apoptosis; Colorectal cancer; Epithelial-mesenchymal transition; Indole-3-acetaldehyde; Tryptophan metabolism |
| تواريخ الأحداث: | Date Created: 20240712 Latest Revision: 20240714 |
| رمز التحديث: | 20240714 |
| مُعرف محوري في PubMed: | PMC11236226 |
| DOI: | 10.4251/wjgo.v16.i6.2697 |
| PMID: | 38994159 |
| قاعدة البيانات: | MEDLINE |
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