Kynurenic acid synthesis and kynurenine aminotransferases expression in colon derived normal and cancer cells

Walczak, Katarzyna; Dąbrowski, Wojciech; Langner, Ewa; Zgrajka, Wojciech; Piłat, Jacek; Kocki, Tomasz; Rzeski, Wojciech; Turski, Waldemar A.

doi:10.3109/00365521.2011.579159

Cited by 76 publications

(79 citation statements)

References 38 publications

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“…Recent results of molecular studies showed that kynurenic acid is a ligand for G protein-coupled receptor 35 (GPR35) and for aryl hydrocarbon receptor (AHR), which are abundantly expressed both in malignant cells and in immune tissues (Wang et al, 2006;DiNatale et al, 2010). Moreover, very recent experimental research disclosed antiproliferative effect of kynurenic acid at micro-and milimolar concentrations against cancer cells in vitro (Walczak et al, 2011). Based on the above considerations we set up a hypothesis that differences in biological behavior between various histologic types of lung cancer may be associated with altered activity of kynurenine metabolic pathway.…”

Section: Introductionmentioning

confidence: 99%

Serum Kynurenic Acid: Possible Association with Invasiveness of Non-small Cell Lung Cancer

Sagan

Kocki²,

Kocki³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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The lung adenocarcinoma is considered more aggressive than other types of non-small cell lung cancer. As metabolites of tryptophan degradation along the kynurenine pathway, including kynurenic acid, have been shown to induce immunosuppression and facilitate escape of tumor cells from immune surveillance, a hypothesis was set up that differences in biological behavior between types of lung cancer may be associated with altered activity of the kynurenine metabolic pathway. The aim of the study was to determine kynurenic acid levels in the serum of patients with bronchial adenocarcinoma for comparison with other types of non-small cell lung cancer. A total of 227 patients with non-small cell lung cancer were enrolled in the study, including 71 with adenocarcinoma and 96 with squamous cell carcinoma. Serum kynurenic acid concentration was determined with use of high performance liquid chromatography and fluorometry. The level of kynurenic acid in the serum of patients with adenocarcinoma was significantly higher than in those with squamous cell lung cancer (107.1 ± 62.8 pmol/ml; 95%CI: 92.4 to 132.3 pmol/ml versus 82.1 ± 47.6 pmol/ml; 95%CI: 78.5 to 91.2 pmol/ml, respectively; p = 0.027). Differences between other histological types of lung cancer were insignificant. We conclude that increased activity of kynurenine metabolic pathway manifested by elevated serum kynurenic acid level may be one of the factors associated with clinically distinct biological behavior of adenocarcinoma, in particular high invasiveness and rapid progression.

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Section: Introductionmentioning

confidence: 99%

Serum Kynurenic Acid: Possible Association with Invasiveness of Non-small Cell Lung Cancer

Sagan

Kocki²,

Kocki³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…The most recent studies by our group have revealed the antiproliferative activity of kynurenic acid, another endogenous tryptophan metabolite, towards cancer cells, including colon cancer cells (Walczak et al, 2011(Walczak et al, , 2012a. Kynurenic acid was found in human body fluids (Kuc et al, 2006(Kuc et al, , 2008Paluszkiewicz et al, 2009;Walczak et al, 2011) as well as in variety of plant and honeybee derived foodstuffs (Turski et al, , 2012Zgrajka et al, 2013). When administered intragastrically, it was absorbed and transported into the peripheral organs, where it was found in concentrations exerting antiproliferative activities in vitro Walczak et al, 2011).…”

Section: Discussionmentioning

confidence: 96%

“…Brown and Price (1956) observed that quinaldic acid may be a tryptophan metabolite arising from the kynurenine pathway. It is proposed that quinaldic acid constitutes a dehydroxylation product of kynurenic acid (Kaihara and Price, 1962), the endogenous tryptophan metabolite, which antiproliferative activity in colon cancer (Walczak et al, 2011), renal cancer (Walczak et al, 2012b) and glioblastoma cells in vitro (Walczak et al, 2014a) has been already stated. Quinaldic acid has been found in animal urea, although at a significantly lower level compared to kynurenic acid.…”

Section: Introductionmentioning

confidence: 98%

Quinaldic acid inhibits proliferation of colon cancer HT-29 cells in vitro: Effects on signaling pathways

Langner

Walczak

Jeleniewicz

et al. 2015

European Journal of Pharmacology

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“…Alternatively, KN may reduce β-catenin expression via its metabolites. KA, a metabolite of the KN pathway of tryptophan degradation, is synthesized in colon-derived normal and cancer cells (43). KA inhibited proliferation of several cancer cell lines including colon cancer cell lines by inhibiting the activation of Akt, ERK1/2 and p38 kinase (43).…”

Section: Discussionmentioning

confidence: 99%

Kynurenine promotes the goblet cell differentiation of HT-29 colon carcinoma cells by modulating Wnt, Notch and AhR signals

Park

Lee

et al. 2018

Oncol Rep

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Abstract.Various amino acids regulate cell growth and differentiation. In the present study, we examined the ability of HT-29 cells to differentiate into goblet cells in RPMI and DMEM which are largely different in the amounts of numerous amino acids. Most of the HT-29 cells differentiated into goblet cells downregulating the stem cell marker Lgr5 when cultured in DMEM, but remained undifferentiated in RPMI. The goblet cell differentiation in DMEM was inhibited by 1-methyl-tryptophan (1-MT), an inhibitor of indoleamine 2,3 dioxygenase-1 which is the initial enzyme in tryptophan metabolism along the kynurenine (KN) pathway, whereas tryptophan and KN induced goblet cell differentiation in RPMI. The levels of Notch1 and its activation product Notch intracytoplasmic domain in HT-29 cells were lower in DMEM than those in RPMI and were increased by 1-MT in both media. HT-29 cells grown in both media expressed β-catenin at the same level on day 2 when goblet cell differentiation was not observed. β-catenin expression, which was increased by 1-MT in both media, was decreased by KN. DMEM reduced Hes1 expression while enhancing Hath1 expression. Finally, aryl hydrocarbon receptor (AhR) activation moderately induced goblet cell differentiation. Our results suggest that KN promotes goblet cell differentiation by regulating Wnt, Notch, and AhR signals and expression of Hes1 and Hath1. IntroductionCell lines are usually maintained in defined media that commonly contain amino acids, vitamins, glucose and inorganic salts for normal cell metabolism. However, the composition of medium formulations vary widely in concentrations of glucose and other metabolic precursors, including amino acids. Thus, many types of cells showed different responses to culture media in regards to proliferation and differentiation. Th17 differentiation was induced more efficiently in Iscove's modified Dulbecco's medium (IMDM) than in RPMI (1). Bone marrow-derived dendritic cells in IMDM expressed higher levels of co-stimulatory and MHC II molecules, compared to the cells generated in RPMI (2). In addition, hepatocyte differentiation and propagation and phenotype of corneal stroma-derived stem cells were modulated by culture media (3,4). Subsequently, the underlying mechanisms of the medium-induced changes in cell proliferation and differentiation have been partially elucidated. Differentiation of Th17 cells was increased by endogenous aryl hydrocarbon receptor (AhR) agonists derived from aromatic amino acids such as tryptophan, which is underrepresented in RPMI compared with IMDM (1). Mesenchymal stem cells co-cultured with AML12 liver cells were able to differentiate into hepatocytelike cells expressing hepatocyte-specific markers including albumin, α-fetoprotein and cytokeratin 18 mRNAs, which were expressed at the initial 7-day culture in DMEM while being expressed during the 7-to 14-day culture in DMEM/ F12 (3). In a study using MDA-MB-231 breast cancer cells, ~25.6% of genes were expressed at significantly different levels in cells grown in MEM, DM...

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Kynurenic acid synthesis and kynurenine aminotransferases expression in colon derived normal and cancer cells

Abstract: Summarizing, this is the first report presenting KYNA synthesis and KAT expression in colon derived normal and cancer cells.

Cited by 76 publications

References 38 publications

Serum Kynurenic Acid: Possible Association with Invasiveness of Non-small Cell Lung Cancer

Serum Kynurenic Acid: Possible Association with Invasiveness of Non-small Cell Lung Cancer

Quinaldic acid inhibits proliferation of colon cancer HT-29 cells in vitro: Effects on signaling pathways

Kynurenine promotes the goblet cell differentiation of HT-29 colon carcinoma cells by modulating Wnt, Notch and AhR signals

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