Abstract
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.
Highlights
Colorectal cancer (CRC) is a growing problem in highly developed countries and the second cause of death among patients diagnosed with cancer in the world [1]
To study the toxicity of 8-hydroxyquinaldic acid, we evaluated the cytotoxic effect of the tested compound on colon epithelial cells in vitro and its activity on development of zebrafish embryos and larvae
We did not observe any significant disorders in embryonic development of zebrafish larvae treated with 8-hydroxyquinaldic acid (0.000001–1 mM)
Summary
Colorectal cancer (CRC) is a growing problem in highly developed countries and the second cause of death among patients diagnosed with cancer in the world [1]. CRC develops for about 10–20 years, late diagnosis is one of the causes of poor treatment efficacy. 8-Hydroxyquinaldic acid was shown to derive from tryptophan metabolism [3]. It is the end-metabolite of tryptophan [4], a product of dehydroxylation of xanthurenic acid [5]. 8-hydroxyquinaldic acid is the analog of kynurenic acid which antiproliferative activity towards various cancer cells was evidenced previously [7,8,9,10]. Structural similarity to kynurenic acid may suggest the potential anti-cancer activity of
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