Department of Medical Biology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950, Lublin, Poland.
Amino Acids. 2012 Oct;43(4):1663-70. doi: 10.1007/s00726-012-1247-5. Epub 2012 Feb 21.
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.
肾脏拥有复杂的酶系统，在色氨酸代谢中起着重要作用。考虑到该器官中一种色氨酸代谢物——犬尿酸（KYNA）的浓度相当高，以及先前报道的其在体外对结肠癌细胞的抗增殖活性，我们测量了人正常和肿瘤肾脏组织中的 KYNA 含量。KYNA 在正常肾组织中的浓度（379.7±39.7 pmol/g 湿重）明显高于肾细胞癌（115.5±20.8 pmol/g 湿重）。在体外实验中，较高的微摩尔和毫摩尔浓度的 KYNA 显著抑制了肾癌细胞 Caki-2 的增殖、DNA 合成和迁移。我们的结果表明，KYNA 可能通过过度表达 p21 Waf1/Cip1 和抑制 Rb 蛋白和 p38 MAPK 的磷酸化来影响细胞周期调节剂和信号通路。总之，KYNA 可能被认为是一种内源性物质，控制肿瘤的生长，或一种化学预防剂。
