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-naphthalene-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-alpha-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 UV-illumination 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.
Konishi
T
T
Department of Radiochemistry and Biophysics, Niigata College of Pharmacy, Japan.
Kagan
V
V
Matsugo
S
S
Packer
L
L
D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology*; D010545:Peroxides / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013113:Spin Labels; D014466:Ultraviolet Rays
D005609:Free Radicals; D006878:Hydroxides; D009281:Naphthalenes; D010545:Peroxides; D011838:Radiation-Sensitizing Agents; D013113:Spin Labels; C067580:N,N'-bis(2-hydroxyperoxy-2-methoxyethyl)-1,4,5,8-naphthalenetetracarboxylic diimide; D017665:Hydroxyl Radical