How Blue Light Activates Furocoumarin Derivatives Triggering Tumor Cell Apoptosis

Furocoumarins comprise natural and synthetic compounds: linear molecules, so called psoralens, and the angular ones, the angelicins. The photobiological effects of furocoumarins plus UVA are mainly related to their capacity to bind DNA and form monoadducts (MAs) and interstrand crosslinks (XLs), mainly with pyrimidine bases. Furthermore, furocoumarins produce ROS that impair cellular functions through lipid peroxidation, oxidation of guanine and strand breaks in nucleic acids, oxidation of proteins and inactivation of enzymes. It is known that the combination of 8-MOP and UVA radiation causes apoptosis of treated leucocytes and may cause preferential apoptosis of activated or abnormal T cells. Moreover, these apoptotic cells may promote immune tolerance, production of antigen-specific regulatory lymphocytes (CD4/8 T, B) and rebalance of immune system. Even though furocoumarins possess high chemotherapeutic potency under UVA and lack toxicity in the dark, genotoxicity, mutagenicity and skin phototoxicity have been observed. 8-MOP was found to photoreact under blue light (BL), leading to less mutagenic lesions in the DNA, that is preferentially MAs over XLs. Furthermore, cells treated with 419 nm light resumed normal growth rates faster than cells which received the same UVA dose.