title: Kynurenic acid in human renal cell carcinoma: its antiproliferative and antimigrative action on Caki-2 cells.
abstract: Kidneys possess a complex enzyme system which plays a major role in tryptophan metabolism. Taking into account a considerably high concentration of one of the tryptophan metabolites, kynurenic acid (KYNA) in this organ and previously reported antiproliferative activity against colon cancer cells in vitro, we measured its content in human normal and tumour kidney tissue. KYNA concentration was considerably higher in normal renal tissue (379.7 ± 39.7 pmol/g wet weight) than in renal cell carcinomas (115.5 ± 20.8 pmol/g wet weight). In in vitro experiments, KYNA in higher micro- and millimolar concentrations significantly inhibited proliferation, DNA synthesis and migration of renal cancer Caki-2 cells. Our results suggest that KYNA may affect cell cycle regulators and signalling pathways through overexpression of p21 Waf1/Cip1 and inhibition of phosphorylation of Rb protein and p38 MAPK. In conclusion, KYNA may be suggested as an endogenous agent, controlling the growth of tumour, or a chemopreventive agent.
authors.affiliation: Department of Medical Biology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950, Lublin, Poland. walczak.ka@gmail.com
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Walczak
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zurawska
authors.forename: Jacek
authors.initials: J
authors.lastname: Kiś
authors.forename: Radosław
authors.initials: R
authors.lastname: Starownik
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zgrajka
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bar
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Turski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Rzeski
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000737:chemistry* / Q000473:pathology; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000473:pathology; D007736:Kynurenic Acid / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016160:Retinoblastoma Protein; D054462:p21-Activated Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D007736:Kynurenic Acid