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.

中文翻译：

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色氨酸代谢物 8-羟基喹哪二酸对结肠直肠癌细胞具有抗增殖和抗迁移作用

色氨酸的最终代谢产物8-羟基喹哪二酸是众所周知的金属螯合剂；然而，它在人类中的作用，特别是在癌症的促进和进展中，尚未完全揭示。重要的是，8-羟基喹哪二酸是犬尿酸的类似物，对各种癌细胞具有明显的抗增殖活性。在这项研究中，我们发现 8-羟基喹哪二酸不仅抑制结肠癌 HT-29 和 LS-180 细胞的增殖和线粒体活性，而且还降低了 HT-29 细胞和 LS 细胞的 DNA 合成高达 90.9% 和 76.1% -180 细胞。8-羟基喹哪二酸诱导细胞周期调节因子（CDK4、CDK6、细胞周期蛋白 D1、细胞周期蛋白 E）和 CDKs 抑制剂（p21 Waf1/Cip1、p27 Kip1）的蛋白质表达发生变化，但其效果取决于所测试的细胞系。而且，8-羟基喹哪二酸抑制结肠癌HT-29和LS-180细胞的迁移并增加β-连环蛋白和E-钙粘蛋白的表达。重要的是，8-羟基喹哪二酸的抗增殖和抗迁移浓度在体外和体内均无毒。我们首次报道了 8-羟基喹哪二酸对结肠癌 HT-29 和 LS-180 细胞的抗增殖和抗迁移活性。