Effect of Tryptophan-Derived AhR Ligands, Kynurenine, Kynurenic Acid and FICZ, on Proliferation, Cell Cycle Regulation and Cell Death of Melanoma Cells—In Vitro Studies

Walczak, Katarzyna; Langner, Ewa; Makuch-Kocka, Anna; Szelest, Monika; Szalast, Karolina; Marciniak, Sebastian; Plech, Tomasz

doi:10.3390/ijms21217946

Cited by 34 publications

(73 citation statements)

References 53 publications

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“…Importantly, kynurenic acid also has antiproliferative and antimigratory properties against various types of cancer cells (reviewed in [ 179 ]) by inhibition of signaling pathways (MAPK, PI3K/Akt) and overexpression of cell cycle regulatory proteins (p21Waf1/Cip1) [ 119 , 201 ]. Moreover, a recent study confirmed the biological activity of kynurenic acid towards melanoma A375 and RPMI-7951 cells [ 202 ].…”

Section: The Role Of Tryptophan-derived Ahr Ligands In Skin Homeosmentioning

confidence: 78%

A New Insight into the Potential Role of Tryptophan-Derived AhR Ligands in Skin Physiological and Pathological Processes

Szelest

Walczak

Plech

2021

IJMS

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The aryl hydrocarbon receptor (AhR) plays a crucial role in environmental responses and xenobiotic metabolism, as it controls the transcription profiles of several genes in a ligand-specific and cell-type-specific manner. Various barrier tissues, including skin, display the expression of AhR. Recent studies revealed multiple roles of AhR in skin physiology and disease, including melanogenesis, inflammation and cancer. Tryptophan metabolites are distinguished among the groups of natural and synthetic AhR ligands, and these include kynurenine, kynurenic acid and 6-formylindolo[3,2-b]carbazole (FICZ). Tryptophan derivatives can affect and regulate a variety of signaling pathways. Thus, the interest in how these substances influence physiological and pathological processes in the skin is expanding rapidly. The widespread presence of these substances and potential continuous exposure of the skin to their biological effects indicate the important role of AhR and its ligands in the prevention, pathogenesis and progression of skin diseases. In this review, we summarize the current knowledge of AhR in skin physiology. Moreover, we discuss the role of AhR in skin pathological processes, including inflammatory skin diseases, pigmentation disorders and cancer. Finally, the impact of FICZ, kynurenic acid, and kynurenine on physiological and pathological processes in the skin is considered. However, the mechanisms of how AhR regulates skin function require further investigation.

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Section: The Role Of Tryptophan-derived Ahr Ligands In Skin Homeosmentioning

confidence: 78%

A New Insight into the Potential Role of Tryptophan-Derived AhR Ligands in Skin Physiological and Pathological Processes

Szelest

Walczak

Plech

2021

IJMS

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“…However, the direct activity of KYN on cancer cell proliferation has not been fully studied. On the contrary, another tryptophan-derived AhR ligand, KYNA, enzymatically formed from KYN, has antiproliferative and antimigratory properties against various types of cancer cells, including glioma, colon, and renal cancer cells [ 9 , 10 , 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, recent research has revealed that selected tryptophan-derived AhR ligands, including KYN and KYNA, possess biological activity toward melanoma A375 and RPMI-7951 cells [ 11 ]. The tryptophan metabolites affected DNA synthesis, cell cycle regulators, and cell death of melanoma cells in vitro.…”

Section: Introductionmentioning

confidence: 99%

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UVB Radiation and Selected Tryptophan-Derived AhR Ligands—Potential Biological Interactions in Melanoma Cells

Walczak

Kazimierczak

Szalast

et al. 2021

IJMS

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Excessive UV exposure is considered the major environmental factor in melanoma progression. Human skin is constantly exposed to selected tryptophan-derived aryl hydrocarbon receptor (AhR) ligands, including kynurenine (KYN) and kynurenic acid (KYNA), as they are endogenously produced and present in various tissues and body fluids. Importantly, recent studies confirmed the biological activity of KYN and KYNA toward melanoma cells in vitro. Thus, in this study, the potential biological interactions between UVB and tryptophan metabolites KYN and KYNA were studied in melanoma A375, SK-MEL-3, and RPMI-7951 cells. It was shown that UVB enhanced the antiproliferative activity of KYN and KYNA in melanoma cells. Importantly, selected tryptophan-derived AhR ligands did not affect the invasiveness of A375 and RPMI-7951 cells; however, the stimulatory effect was observed in SK-MEL-3 cells exposed to UVB. Thus, the effect of tryptophan metabolites on metabolic activity, cell cycle regulation, and cell death in SK-MEL-3 cells exposed to UVB was assessed. In conclusion, taking into account that both UVB radiation and tryptophan-derived AhR ligands may have a crucial effect on skin cancer formation and progression, these results may have a significant impact, revealing the potential biological interactions in melanoma cells in vitro.

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“…Due to the pivotal importance of milk protein in human health, investigating supplementation with AAs (e.g., methionine, lysine) as the main nutrients that can positively stimulate milk protein synthesis in mammary epithelial cells (MEC) has been a priority as of late [ 2 ]. Tryptophan (Trp), known as a conditional EAA [ 3 ], can be supplemented in the diets of animals and humans when targeting maximal production, cell growth, and proliferation [ 4 , 5 , 6 ]. Furthermore, Trp has been widely introduced as a mostly harmless supplement for humans to cope with health issues such as stress and depression.…”

Section: Introductionmentioning

confidence: 99%

Supplementing with L-Tryptophan Increases Medium Protein and Alters Expression of Genes and Proteins Involved in Milk Protein Synthesis and Energy Metabolism in Bovine Mammary Cells

Conejos

Lee

Kim

et al. 2021

IJMS

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The objective of this study was to investigate the effects of supplementing with L-tryptophan (L-Trp) on milk protein synthesis using an immortalized bovine mammary epithelial (MAC-T) cell line. Cells were treated with 0, 0.3, 0.6, 0.9, 1.2, and 1.5 mM of supplemental L-Trp, and the most efficient time for protein synthesis was determined by measuring cell, medium, and total protein at 0, 24, 48, 72, and 96 h. Time and dose tests showed that the 48 h incubation time and a 0.9 mM dose of L-Trp were the optimal values. The mechanism of milk protein synthesis was elucidated through proteomic analysis to identify the metabolic pathway involved. When L-Trp was supplemented, extracellular protein (medium protein) reached its peak at 48 h, whereas intracellular cell protein reached its peak at 96 h with all L-Trp doses. β-casein mRNA gene expression and genes related to milk protein synthesis, such as mammalian target of rapamycin (mTOR) and ribosomal protein 6 (RPS6) genes, were also stimulated (p < 0.05). Overall, there were 51 upregulated and 59 downregulated proteins, many of which are involved in protein synthesis. The results of protein pathway analysis showed that L-Trp stimulated glycolysis, the pentose phosphate pathway, and ATP synthesis, which are pathways involved in energy metabolism. Together, these results demonstrate that L-Trp supplementation, particularly at 0.9 mM, is an effective stimulus in β-casein synthesis by stimulating genes, proteins, and pathways related to protein and energy metabolism.

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Effect of Tryptophan-Derived AhR Ligands, Kynurenine, Kynurenic Acid and FICZ, on Proliferation, Cell Cycle Regulation and Cell Death of Melanoma Cells—In Vitro Studies

Cited by 34 publications

References 53 publications

A New Insight into the Potential Role of Tryptophan-Derived AhR Ligands in Skin Physiological and Pathological Processes

A New Insight into the Potential Role of Tryptophan-Derived AhR Ligands in Skin Physiological and Pathological Processes

UVB Radiation and Selected Tryptophan-Derived AhR Ligands—Potential Biological Interactions in Melanoma Cells

Supplementing with L-Tryptophan Increases Medium Protein and Alters Expression of Genes and Proteins Involved in Milk Protein Synthesis and Energy Metabolism in Bovine Mammary Cells

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