Kynurenic acid enhances expression of p21 Waf1/Cip1 in colon cancer HT-29 cells

Walczak, Katarzyna; Turski, Waldemar A.; Rzeski, Wojciech

doi:10.1016/s1734-1140(12)70870-8

Cited by 31 publications

(45 citation statements)

References 20 publications

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“…Akt is also a negative regulator of CDK inhibitors p21 Waf1/Cip1 and p27 Kip1 (Gesbert et al 2000; Zhou et al 2001). The results suggested that Akt inhibition in KYNA-treated HT-29 cells might result in previously reported overexpression of p21 Waf1/Cip1 (Walczak et al 2012a). Interestingly, KYNA modulated also phosphorylation of GSK3β in HT-29 cells.…”

Section: Discussionsupporting

confidence: 56%

“…Previous studies indicated antiproliferative properties of KYNA towards colon adenocarcinoma HT-29, Caco-2 and LS-180 cells (Walczak et al 2011, 2012a), renal cell carcinoma Caki-2 cells (Walczak et al 2012b) and glioblastoma T98G cells (Walczak et al 2014). However, the exact molecular mechanism of antiproliferative activity of KYNA has not been fully revealed.…”

Section: Discussionmentioning

confidence: 99%

“…There are only few data concerning the potential molecular mechanisms of antiproliferative activity of KYNA in cancer cells. The inhibitory properties of KYNA might be related to overexpression of cyclin-dependent kinases (CDK) inhibitor p21 Waf1/Cip1 (Walczak et al 2012a, b). KYNA was also reported as a potential inhibitor of p38 kinase in renal cancer cells (Walczak et al 2012b); however, the exact molecular interactions of KYNA with signaling pathways in colon cancer cells have not been studied to date.…”

Section: Introductionmentioning

confidence: 99%

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Kynurenic acid inhibits colon cancer proliferation in vitro: effects on signaling pathways

2014

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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.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Kynurenic acid inhibits colon cancer proliferation in vitro: effects on signaling pathways

2014

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“…Twenty five µl of RT-PCR mixture contained 10 µl of RNase free H O, 5 µl of 5 × buffer, 2 µl of 10 mM dNTP, 100 nmol/l of each primer and 1 µg RNA. The following primers were employed in semi-quantitative RT-PCR analysis: p21 [24,30] forward primer: 5'-AGCAGAGGAAGA-CCATGTGGAC-3' and p21 reverse primer: 5'-TTT-CGACCCTGAGA GTCTCCAG-3' p53 forward primer: 5'-TGCGTGTGGAGTATTTG GATG-3' and p53 reverse primer: 5'-TGGTACAGTCAGAGCCAA-CCAG-3'; b-actin [5] forward primer: 5'-AACAGT-CCGCCTAGAAGCAC-3' and b-actin reverse primer: 5'-CGTTGACATCGTAAAGACC-3'. The amplified products were size-fractionated by electrophoresis on 1.5% agarose gel, and analyzed by a FluorChem 8000 system with a software (Alpha Innotech, Santa Clara, CA, USA).…”

Section: Semiquantitative Rt-pcrmentioning

confidence: 99%

Anisomycin suppresses Jurkat T cell growth by the cell cycle-regulating proteins

Xing

Tang

et al. 2013

Pharmacological Reports

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Abstract:Background: Recent studies have shown that anisomycin significantly inhibits mammalian cell proliferation, but its mechanism remains unclear. In this study, Jurkat T cells were used to first explore a relationship between effect of anisomycin on them and alteration of cell cycle-regulating proteins. Methods: Cell colony formation, CCK-8 assay, flow cytometry, RT-PCR and western blot were employed to evaluate correlation of ten cell cycle-regulating proteins with suppression of the cell proliferation and arrest of the cell cycle by anisomycin. Results: Our data showed that anisomycin inhibited the colony-formation and proliferation of Jurkat T cells in a dose-dependent manner, and arrested the cells into S and G2/M phases with the production of sub-diploid cells. The levels of P21, P-P27 and P53/P-P53 reached their peaks 4 h after anisomycin treatment, presenting a positive correlation with anisomycin concentration, and P16, P-P21, P27, P57, P73/P-P73 and P-Rb changed little with the prolonged exposure time or increased concentrations of anisomycin. But the level of Rb protein was increased at 24 h after the treatment of anisomycin. The expression of an inverted CCAAT box binding protein (ICBP90) in Jurkat T cells came to decrease 12 h after the treatment of anisomycin, presenting a negative correlation with anisomycin concentration. Subsequently, the expression of P-CDK2 was also decreased at 24 h, presenting an obviously negative correlation, whereas P-CDK1 showed no differences among the differently treated Jurkat T cells. Furthermore, the level of P21 and P53 mRNA was increased with the enhanced concentrations of anisomycin. Conclusion:The results indicate that anisomycin may activate the P53/P21/P27 signaling to decrease the expression of ICBP90, inhibit expression of P-CDK2 to block the cells into S and G2/M phases, and finally result in proliferation inhibition of Jurkat T cells.

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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).…”

Section: Discussionmentioning

confidence: 99%

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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Kynurenic acid enhances expression of p21 Waf1/Cip1 in colon cancer HT-29 cells

Cited by 31 publications

References 20 publications

Kynurenic acid inhibits colon cancer proliferation in vitro: effects on signaling pathways

Kynurenic acid inhibits colon cancer proliferation in vitro: effects on signaling pathways

Anisomycin suppresses Jurkat T cell growth by the cell cycle-regulating proteins

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

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