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Kynurenic acid inhibits proliferation and migration of human glioblastoma T98G cells
Kynurenic acid (KYNA), tryptophan metabolite synthesized in the kynurenine pathway, is an endogenous antagonist of α-7 nicotinic receptor and all ionotropic glutamate receptors: N-methyl-d-aspartate (NMDA) receptor, α-amino-3-hydroxy-5-methyl-4-isoxasole propionate (AMPA) receptor and kainate recept...
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Published in: | Pharmacological reports 2014-02, Vol.66 (1), p.130-136 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Kynurenic acid (KYNA), tryptophan metabolite synthesized in the kynurenine pathway, is an endogenous antagonist of α-7 nicotinic receptor and all ionotropic glutamate receptors: N-methyl-d-aspartate (NMDA) receptor, α-amino-3-hydroxy-5-methyl-4-isoxasole propionate (AMPA) receptor and kainate receptor. The antiproliferative activity of KYNA toward colon and renal cancer cells has recently been discovered. The aim of the study was to verify whether human Glioblastoma tumors contain KYNA and if KYNA influences glioma cell proliferation and migration.
KYNA content in Glioblastoma tumor samples was determined using HPLC. Proliferation of human glioblastoma T98G cells was measured by means of MTT and BrdU assays. Wound assay was used to evaluate the effect of KYNA on cancer cell migration.
KYNA was detected in all tested Glioblastoma tumor samples (100.3±17.6pmol/g wet weight). In a series of experiments the antiproliferative activity of KYNA against T98G cells was revealed (IC50=1.3mM). Moreover, KYNA reversed the stimulatory effect of glutamate on glioma cell proliferation and enhanced antiproliferative effect of glutamate receptor antagonists MK801 and GYKI 52466. Next, KYNA at concentrations much lower than those needed to reduce cell proliferation elicited a prominent inhibitory effect on glioma cell motility. Moreover, co-incubation of temozolomide, a drug commonly used in antiglioblastoma therapy, with KYNA gave a superior effect than each of the substances applied alone.
We demonstrate the antiproliferative and antimigrative potential of KYNA against glioma cells in vitro. |
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ISSN: | 1734-1140 2299-5684 |
DOI: | 10.1016/j.pharep.2013.06.007 |