Quinaldic acid inhibits proliferation of colon cancer HT-29 cells in vitro: Effects on signaling pathways

摘要

Quinaldic acid is presumed to be a derivative of kynurenic acid, a tryptophan metabolite with proven antiproliferative activity towards cancer cells in vitro. The aim of present study was to evaluate the activity of quinaldic acid in colon cancer cells. The antiproliferative potential of quinaldic acid was assessed in HT-29, LS180 and Caco-2 cells. Suppression of metabolic activity (IC50 of 0.5 mM for HT-29 and LS180 cells, 0.9 mM for Caco-2 cells) and DNA synthesis (IC50 of 2.7, 4.3, 2 mM for HT-29, LS180 and Caco-2 cells, respectively) were observed in all tested cell lines. It is noteworthy that quinaldic acid in antiproliferative concentrations was non-toxic to normal colon epithelium CCD 841 CoTr cells. Concomitantly, alterations in several signaling pathways in HT-29 cells were observed. Quinaldic acid led to changes in the phosphorylation level of extracellular-signal-regulated kinase (ERK) 1/2, p38, cAMP response element-binding protein (CREB) and Ala (protein kinase B) kinases. Moreover, changes in the CREB transcription factor were also found at the gene expression level. Antiproliferative activity and signaling pathways modulatory potential of quinaldic acid in colon cancer cells in vitro has been stated. (C) 2015 Elsevier B.V. All rights reserved.