title: Quinaldic acid inhibits proliferation of colon cancer ht-29 cells in vitro: effects on signaling pathways.
abstract: 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 0.5mM for HT-29 and LS180 cells, 0.9mM for Caco-2 cells) and DNA synthesis (IC50 of 2.7, 4.3, 2mM 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 Akt (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.
authors: Department of Pharmacology, Medical University in Lublin, Chodźki 4a, 20-093 Lublin, Poland; Department of Medical Biology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-090 Lublin, Poland. Electronic address: ewa.langner@gmail.com.
authors: Ewa
authors: E
authors: Langner
authors: Department of Pharmacology, Medical University in Lublin, Chodźki 4a, 20-093 Lublin, Poland.
authors: Katarzyna
authors: K
authors: Walczak
authors: Department of Biochemistry and Molecular Biology, Medical University in Lublin, Chodźki 1, 20-093 Lublin, Poland.
authors: Witold
authors: W
authors: Jeleniewicz
authors: Department of Experimental and Clinical Pharmacology, Medical University in Lublin, Jaczewskiego 8, 20-090 Lublin, Poland.
authors: Waldemar A
authors: WA
authors: Turski
authors: Department of Pharmacology, Medical University in Lublin, Chodźki 4a, 20-093 Lublin, Poland.
authors: Grażyna
authors: G
authors: Rajtar
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D017362:Cyclic AMP Response Element-Binding Protein; D011804:Quinolines; D020928:Mitogen-Activated Protein Kinases; C008898:quinaldic acid
keywords: Cancer cells proliferation; Colon cancer; Kynurenic acid; Quinaldic acid; Quinaldic acid (PubChem CID: 7124)