Title: 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.

Authors: Justiniano, Rebecca; de Faria Lopes, Lohanna; Perer, Jessica; Hua, Anh; Park, Sophia L; Jandova, Jana; Baptista, Maurício S; Wondrak, Georg T

Published In Photochem Photobiol, (2021 01)

Abstract: UV-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 endogenous aryl hydrocarbon receptor agonist, displays activity as a nanomolar sensitizer of photooxidative stress, causing the photodynamic elimination of human melanoma and nonmelanoma skin cancer cells in vitro and in vivo. FICZ is an efficient UVA/Visible photosensitizer having absorbance maximum at 390 nm (ε = 9180 L mol-1  cm-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 cm-2 ) 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 cells in vivo.

PubMed ID: 32767762

MeSH Terms: Animals; Carbazoles; Carcinoma, Squamous Cell/drug therapy*; Cell Death; Cell Line, Tumor; Epidermis/drug effects; Epidermis/radiation effects; Humans; Keratinocytes/drug effects; Keratinocytes/radiation effects; Melanoma/drug therapy*; Mice; Mitochondria; Oxidative Stress; Photochemotherapy*; Photosensitizing Agents/chemistry; Photosensitizing Agents/pharmacology*; Skin Neoplasms/drug therapy*; Tryptophan/analogs & derivatives*; Ultraviolet Therapy