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A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells.
Walczak, Katarzyna; Langner, Ewa; Szalast, Karolina; Makuch-Kocka, Anna; Pozarowski, Piotr; Plech, Tomasz.
Afiliación
  • Walczak K; Department of Pharmacology, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland.
  • Langner E; Department of Pharmacology, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland.
  • Szalast K; Department of Medical Biology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland.
  • Makuch-Kocka A; Department of Pharmacology, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland.
  • Pozarowski P; Department of Pharmacology, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland.
  • Plech T; Chair and Department of Clinical Immunology, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland.
Molecules ; 25(7)2020 Apr 03.
Article en En | MEDLINE | ID: mdl-32260268
8-Hydroxyquinaldic acid, the end-metabolite of tryptophan, is well-known metal chelator; however, its role in humans, especially in cancer promotion and progression, has not been fully revealed. Importantly, 8-hydroxyquinaldic acid is the analog of kynurenic acid with evidenced antiproliferative activity towards various cancer cells. In this study, we revealed that 8-hydroxyquinaldic acid inhibited not only proliferation and mitochondrial activity in colon cancer HT-29 and LS-180 cells, but it also decreased DNA synthesis up to 90.9% for HT-29 cells and 76.1% for LS-180 cells. 8-Hydroxyquinaldic acid induced changes in protein expression of cell cycle regulators (CDK4, CDK6, cyclin D1, cyclin E) and CDKs inhibitors (p21 Waf1/Cip1, p27 Kip1), but the effect was dependent on the tested cell line. Moreover, 8-hydroxyquinaldic acid inhibited migration of colon cancer HT-29 and LS-180 cells and increased the expression of ß-catenin and E-cadherin. Importantly, antiproliferative and anti-migratory concentrations of 8-hydroxyquinaldic acid were non-toxic in vitro and in vivo. We reported for the first time antiproliferative and anti-migratory activity of 8-hydroxyquinaldic acid against colon cancer HT-29 and LS-180 cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Proteínas de Ciclo Celular / Ácido Quinurénico Límite: Humans Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Proteínas de Ciclo Celular / Ácido Quinurénico Límite: Humans Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Suiza