Kynurenic acid inhibits colon cancer proliferation in vitro: effects on signaling pathwaysReportar como inadecuado

Kynurenic acid inhibits colon cancer proliferation in vitro: effects on signaling pathways - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Amino Acids

, Volume 46, Issue 10, pp 2393–2401

First Online: 11 July 2014Received: 21 March 2014Accepted: 17 June 2014DOI: 10.1007-s00726-014-1790-3

Cite this article as: Walczak, K., Turski, W.A. & Rajtar, G. Amino Acids 2014 46: 2393. doi:10.1007-s00726-014-1790-3


Kynurenic acid KYNA, a tryptophan metabolite, inhibits proliferation of several cancer cell lines including colon cancer, renal cancer and glioblastoma cells. Previous studies reported that inhibitory properties of KYNA may be related to interactions of KYNA with cell cycle regulators and signaling proteins. However, the exact molecular interaction of KYNA with signaling pathways in colon cancer cells has not been studied to date. The molecular mechanism of KYNA activity towards colon cancer cells may be of great importance taking into consideration that KYNA is present in several tissues and physiological fluids, including gastrointestinal tract, and it is also present in various products of human diet. In this study, the inhibitory effect of KYNA on activation of phosphoinositide 3-kinase-Akt PI3K-Akt and mitogen-activated protein kinase MAPK signaling pathways in colon adenocarcinoma HT-29 cells was revealed. KYNA decreased phosphorylation of Akt, ERK 1-2 and p38 kinases in HT-29 cells. Interestingly, the study revealed also unexpected effect of KYNA on Wnt pathway in HT-29 cells. KYNA in millimolar concentrations increased protein expression of β-catenin. However, the nuclear translocation of β-catenin in HT-29 cells exposed to KYNA was not observed. Moreover, KYNA 1 mM increased antiproliferative properties of inhibitors of signaling pathways: wortmannin, PD98059, SB202190 and IWR-1. Taking into consideration these results, KYNA may be seen as a potential chemopreventive agent in colon cancer or supportive agent in standard cancer chemotherapy. However, the interactions between KYNA, Wnt signaling pathway and β-catenin need further studies to exclude potential effect of KYNA on colon carcinogenesis.

KeywordsKynurenic acid Colon cancer Signaling pathways PI3K-Akt pathway MAPK Wnt pathway AbbreviationsAhRAryl hydrocarbon receptor

CDKCyclin-dependent kinases

DMEMDulbecco’s modified Eagle-s medium

DMSODimethyl sulfoxide

ECACCEuropean Collection of Cell Cultures

ERKExtracellular signal-regulated kinases

FBSFetal bovine serum

FITCFluorescein isothiocyanate

GPR35G-protein coupled receptor 35

KYNAKynurenic acid

MAPKMitogen-activated protein kinase

mTORMammalian target of rapamycin

MTT3-4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide

PBSPhosphate buffered saline

PI3KPhosphoinositide 3-kinase

PTENPhosphatase and tensin homolog

PVDFPolyvinylidene difluoride

SDSSodium dodecyl sulphate

SEMStandard error of the mean

TBSTris-buffered saline

Download fulltext PDF

Autor: Katarzyna Walczak - Waldemar A. Turski - Grażyna Rajtar


Documentos relacionados