title: Kynurenic acid synthesis and kynurenine aminotransferases expression in colon derived normal and cancer cells.
abstract: BACKGROUND
  Kynurenic acid (KYNA), a tryptophan metabolite, was found in human saliva, gastric juice, bile, pancreatic juice and mucus of rat small intestine.
  
  
  METHODS
  KYNA content in mucus aspirated from human caecum or colon ascendens and KYNA production in colon epithelial and cancer cells were determined using HPLC. Moreover, biological properties of KYNA and kynurenine aminotransferases (KATs) expression in colon epithelial and colon cancer cells were studied.
  
  
  RESULTS
  Considerably higher KYNA concentration was detected in samples from patients diagnosed with colon carcinoma (269.40 ± 107.00 pmol/ml, N = 4), Adenoma tubulovillosum (200.50 ± 36.72, N = 10) or Adenoma tubulare (243.50 ± 38.09, N = 9) than in control group (82.22 ± 7.61 pmol/ml, N = 30). Moreover, colon epithelium CCD 841 CoTr cells actively synthesized KYNA in a concentration- and time-dependent manner. This process was decreased by aminooxyacetic acid and L-glutamate in opposite to 4-aminopyridine treatment. Interestingly, KYNA production in colon cancer cells (HT-29 1.39 ± 0.27, LS-180 1.18 ± 0.15 and Caco-2 4.21 ± 0.30 pmol/1 x 10(5) cells/2 h) was considerably higher in comparison to normal colon epithelial cells (0.70 ± 0.07 pmol/1 x 10(5) cells/2 h). However, KATs I and II were expressed at similar level in both colon epithelium and cancer cells. Furthermore, KYNA exerted an antiproliferative effect at higher micro- and millimolar concentrations against colon cancer cells with the IC(50) of 0.9, 0.2 and 1.2 mM for HT-29, LS-180 and Caco-2 cells, respectively.
  
  
  CONCLUSIONS
  Summarizing, this is the first report presenting KYNA synthesis and KAT expression in colon derived normal and cancer cells.
authors: Department of Medical Biology, Institute of Agricultural Medicine, Lublin, Poland.
authors: Katarzyna
authors: K
authors: Walczak
authors: Wojciech
authors: W
authors: Dąbrowski
authors: Ewa
authors: E
authors: Langner
authors: Wojciech
authors: W
authors: Zgrajka
authors: Jacek
authors: J
authors: Piłat
authors: Tomasz
authors: T
authors: Kocki
authors: Wojciech
authors: W
authors: Rzeski
authors: Waldemar A
authors: WA
authors: Turski