UV induces oxy- and chromanoxyl free radicals in microsomes by a new photosensitive organic hydroperoxide, N,N′-bis(2-hydroperoxy-2-methoxyethyl)-1,4,5,8-naphtalene-tetra-carboxylic-diimide

Low oxygen tension, a high content of reducing equivalents and endogenous vitamin E are responsible for the resistance of cancer cells to oxidative stress-based therapy. N,N′-bis(2-hydroperoxy-2-methoxyethyl)-1,4,5,8-naphtalene-tetra-carboxylic-diimide (NP-III), capable to release radicals both in the absence and in the presence of oxygen upon UV-illumination, is a new potential anticancer agent. UV-induced reactions of NP-III in rat liver microsomes were studied under aerobic and anaerobic conditions with (i) vitamin E homologue, chromanol-α-C-6 having a shorter (6-carbon) hydrocarbon side chain and higher antioxidant activity, and (ii) the spin-trap 5,5-dimethyl-1-pyrroline-1-oxide, DMPO. UV-induced generation of chromanoxyl radicals was observed in the presence of NP-III under aerobic conditions, which was SOD+catalase sensitive. Hydroxyl-, superoxide- and alkoxyl-radical DMPO adducts were found upon UVillumination of NP-III under aerobic conditions and only hydroxyl-radical adducts under anaerobic conditions. The light-dependent generation of oxy- and chromanoxyl free radicals and depletion of endogenous antioxidants suggests to be a promising strategy to overcome the inherent resistance of tumor cells to oxidative stress.