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 × 10⁵ cells/2 h) was considerably higher in comparison to normal colon epithelial cells (0.70 ± 0.07 pmol/1 × 10⁵ 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 milimolar concentrations against colon cancer cells with the IC₅₀ of 0.9, 0.2 and 1.2 mM for HT-29, LS-180 and Caco-2 cells, respectively. Conclusion. Summarizing, this is the first report presenting KYNA synthesis and KAT expression in colon derived normal and cancer cells.

Key Words::

• Colon epithelium
• colon cancer
• kynurenic acid
• kynurenine aminotransferases
• proliferation

Acknowledgements

This study was supported in part by Foundation for Polish Science. We thank Małgorzata Cyranka (Independent Laboratory of Molecular Biology, Institute of Agricultural Medicine, Lublin, Poland) for microscopic analysis of cell cultures.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.