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.
