The Endogenous Tryptophan ‐derived Photoproduct 6‐formylindolo[3,2‐b]carbazole (FICZ) Is a Nanomolar Photosensitizer That Can Be Harnessed for the Photodynamic Elimination of Skin Cancer Cells in Vitro and in Vivo

ABSTRACTUV ‐chromophores contained in human skin may act as endogenous sensitizers of photooxidative stress and can be employed therapeutically for the photodynamic elimination of malignant cells. Here we report that 6‐formylindolo[3,2‐b]carbazole (FICZ), a tryptophan‐derived photoproduct and endoge nous aryl hydrocarbon receptor agonist, displays activity as a nanomolar sensitizer of photooxidative stress, causing the photodynamic elimination of human melanoma and nonmelanoma skin cancer cellsin vitro andin vivo. FICZ is an efficient UVA/Visible photosensitizer having absorbance maximum at 390 nm ( ε = 9180 Lmol‐1cm‐1), and fluorescence and singlet oxygen quantum yields of 0.15 and 0.5, respectively, in methanol. In a panel of cultured human squamous cell  carcinoma and melanoma skin cancer cells (SCC‐25, HaCaT‐ras II‐4, A375, G361, LOX), photodynamic induction of cell death was elicited by the combined action of solar simulated UVA (6.6 J/cm2) and  FICZ (≥ 10 nM), preceded by the induction of oxidative stress as substantiated by MitoSOX Red fluorescence microscopy, comet detection of Fpg‐sensitive oxidative genomic lesions, and upregulated stress response gene expression (HMOX1,  HSPA1A,HSPA6). In SKH1 ‘high‐risk’ mouse skin, an experimental FICZ/UVA photodynamic treatment regimen blocked the progression of UV‐induced tumorigenesis suggesting feasibility of harnessing FICZ for the photooxidative elimination of malignant cellsin vi...
Source: Photochemistry and Photobiology - Category: Science Authors: Tags: RESEARCH ARTICLE Source Type: research