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.
Highlights
The skin is constantly exposed to various substances with pro- and anti-carcinogenic potential
To determine the effect of L-KYN, kynurenic acid (KYNA) and FICZ on proliferation of human melanocytes and melanoma cells, human adult primary epidermal melanocytes (HEMa), A375 and RPMI7951 cells were exposed to serial dilutions of tested tryptophan-derived aryl hydrocarbon receptor (AhR) ligands
We showed that tryptophan-derived AhR ligands, including KYN, KYNA and FICZ, do not stimulate promotion and progression of melanoma in vitro, but simultaneously the tested compounds in higher concentrations inhibited proliferation and stimulated cell death of melanoma cells
Summary
The skin is constantly exposed to various substances with pro- and anti-carcinogenic potential. Environmental pollution, skin care products and UV radiation can affect various processes in the skin. Environmental UV exposure, fair color of skin and hair, family history of melanoma and a high number of melanocytic nevi are well-characterized risk factors for developing melanoma [1]. Melanoma is rare among all types of skin cancers (less than 5%) but the most aggressive [2,3]. A median survival rate of patients with metastatic melanoma is approximately 6 months [2]. A poor prognosis for patients with advanced melanoma results from rapid metastasis, resistance to anti-cancer therapies and immunosuppressive abilities. There are two main strategies in melanoma prevention and treatment: inhibition of melanocyte-to-melanoma transition and inhibition of melanoma metastasis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
