Planta Med 2012; 78 - PC2
DOI: 10.1055/s-0032-1320351

Isolation of malassezia metabolites with powerful AHR activity from human skin. is there implication in skin cancer development?

P Magiatis 1, 2, E Melliou 1, 3, N Mexia 1, M Denison 2, I Bassukas 4, G Gaitanis 4
  • 1Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, University of Athens, 15771 Greece
  • 2Department of Environmental Toxicology
  • 3Department of Food Science and Technology, University of California, Davis, CA 95616
  • 4Department of Skin and Venereal Diseases, Medical School, University of Ioannina, Greece

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.