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.