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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
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 21, Iss 7946, p 7946 (2020), Volume 21, Issue 21
- Publication Year :
- 2020
- Publisher :
- MDPI, 2020.
-
Abstract
- Tryptophan metabolites: kynurenine (KYN), kynurenic acid (KYNA) and 6-formylindolo[3,2-b]carbazole (FICZ) are considered aryl hydrocarbon receptor (AhR) ligands. AhR is mainly expressed in barrier tissues, including skin, and is involved in various physiological and pathological processes in skin. We studied the effect of KYN, KYNA and FICZ on melanocyte and melanoma A375 and RPMI7951 cell toxicity, proliferation and cell death. KYN and FICZ inhibited DNA synthesis in both melanoma cell lines, but RPMI7951 cells were more resistant to pharmacological treatment. Tested compounds were toxic to melanoma cells but not to normal human adult melanocytes. Changes in the protein level of cyclin D1, CDK4 and retinoblastoma tumor suppressor protein (Rb) phosphorylation revealed different mechanisms of action of individual AhR ligands. Importantly, all tryptophan metabolites induced necrosis, but only KYNA and FICZ promoted apoptosis in melanoma A375 cells. This effect was not observed in RPMI7951 cells. KYN, KYNA and FICZ in higher concentrations inhibited the protein level of AhR but did not affect the gene expression. To conclude, despite belonging to the group of AhR ligands, KYN, KYNA and FICZ exerted different effects on proliferation, toxicity and induction of cell death in melanoma cells in vitro.
- Subjects :
- Kynurenic Acid
Retinoblastoma Protein
lcsh:Chemistry
chemistry.chemical_compound
Kynurenic acid
Basic Helix-Loop-Helix Transcription Factors
Cyclin D1
Phosphorylation
lcsh:QH301-705.5
Spectroscopy
Kynurenine
biology
Melanoma
Cell Cycle
General Medicine
Cell cycle
Computer Science Applications
Gene Expression Regulation, Neoplastic
cell death
Melanocytes
Programmed cell death
Cell Survival
proliferation
Carbazoles
Catalysis
Article
Inorganic Chemistry
Cell Line, Tumor
medicine
melanoma
Humans
tryptophan
Physical and Theoretical Chemistry
Molecular Biology
Cell Proliferation
Organic Chemistry
AhR
Cyclin-Dependent Kinase 4
Aryl hydrocarbon receptor
medicine.disease
FICZ
chemistry
lcsh:Biology (General)
lcsh:QD1-999
Receptors, Aryl Hydrocarbon
Apoptosis
biology.protein
Cancer research
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 21
- Issue :
- 21
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....e00a2c0551f9cb9001d91032d27308b2