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Open AccessArticle

A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells

1
Department of Pharmacology, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland
2
Department of Medical Biology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland
3
Chair and Department of Clinical Immunology, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland
*
Authors to whom correspondence should be addressed.
Academic Editor: Bartosz Tylkowski
Molecules 2020, 25(7), 1655; https://doi.org/10.3390/molecules25071655
Received: 15 March 2020 / Revised: 31 March 2020 / Accepted: 2 April 2020 / Published: 3 April 2020
(This article belongs to the Special Issue Anticancer Drug Discovery and Development)
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 β-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. View Full-Text
Keywords: colorectal cancer; metastasis; Wnt/β-catenin pathway; cell cycle regulators; zebrafish colorectal cancer; metastasis; Wnt/β-catenin pathway; cell cycle regulators; zebrafish
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Walczak, K.; Langner, E.; Szalast, K.; Makuch-Kocka, A.; Pożarowski, P.; Plech, T. A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells. Molecules 2020, 25, 1655.

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