title: Kynurenic acid inhibits proliferation and migration of human glioblastoma T98G cells.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  KYNA was detected in all tested Glioblastoma tumor samples (100.3 ± 17.6 pmol/g wet weight). In a series of experiments the antiproliferative activity of KYNA against T98G cells was revealed (IC(50) = 1.3 mM). 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.
  
  
  CONCLUSIONS
  We demonstrate the antiproliferative and antimigrative potential of KYNA against glioma cells in vitro.
authors.affiliation: Department of Pharmacology, Medical University, Lublin, Poland; Department of Medical Biology, Institute of Rural Health, Lublin, Poland. Electronic address: walczak.ka@gmail.com.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Walczak
authors.affiliation: Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Deneka-Hannemann
authors.affiliation: Department of Neurosurgery and Paediatric Neurosurgery, Medical University, Lublin, Poland.
authors.forename: Bożena
authors.initials: B
authors.lastname: Jarosz
authors.affiliation: Department of Toxicology, Institute of Rural Health, Lublin, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zgrajka
authors.affiliation: Department of Neurosurgery and Paediatric Neurosurgery, Medical University, Lublin, Poland.
authors.forename: Filip
authors.initials: F
authors.lastname: Stoma
authors.affiliation: Department of Neurosurgery and Paediatric Neurosurgery, Medical University, Lublin, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Trojanowski
authors.affiliation: Department of Toxicology, Institute of Rural Health, Lublin, Poland; Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland.
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Turski
authors.affiliation: Department of Medical Biology, Institute of Rural Health, Lublin, Poland; Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Rzeski
mesh_terms: D000328:Adult; D000368:Aged; D001569:Benzodiazepines / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D007736:Kynurenic Acid / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
chemical_list: C061950:GYKI 52466; D001569:Benzodiazepines; D018698:Glutamic Acid; D007736:Kynurenic Acid
keywords: Glioma; Glutamate antagonists; Kynurenic acid; Proliferation