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DOI: 10.1055/s-0032-1320351
Isolation of malassezia metabolites with powerful AHR activity from human skin. is there implication in skin cancer development?
Malassezia is a genus of human symbiotic yeasts that can become pathogenic under insufficiently understood conditions and have been correlated with skin diseases like seborrheic dermatitis, pityriasis versicolor, dandruff etc affecting a major part of the global population. We have recently proposed that Malassezia could be a factor that promotes basal cell cancer due to the production of Aryl hydrocarbon Receptor (AhR) inducers that can modify the immune system response and hyperactivate the CYP enzymes. When we investigated skin extracts from patients they showed 100–1000 times stronger AhR inducing activity than the skin extracts of healthy volunteers. Chemical analysis of the patients' extracts by LC/MS/MS revealed for the first time significant amounts of compounds like 6-formylindolo[3,2-b]carbazole (FICZ), indolo[3,2-b]carbazole (ICZ), malassezin, indirubin and pityriacitrin in human skin. The same compounds were also identified and isolated from Malassezia furfur extracts revealing their unequivocal origin. Indirubin and FICZ were found to be the two most active known AhR ligands even stronger than dioxin. Evaluation of their AhR inducing activity in human HepG2 cells transfected with a luciferase reporter gene at 6h showed EC50s 3.8×10-11 and 9.9×10-11 M respectively, in comparison with 5.2×10-10 M for dioxin.