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

Biochem Biophys Res Commun. 1991 Feb 28;175(1):129-33. doi: 10.1016/s0006-291x(05)81210-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aerobiosis
  • Anaerobiosis
  • Animals
  • Electron Spin Resonance Spectroscopy
  • Free Radicals
  • Hydroxides
  • Hydroxyl Radical
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism*
  • Naphthalenes / pharmacology*
  • Peroxides / pharmacology*
  • Radiation-Sensitizing Agents / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Spin Labels
  • Ultraviolet Rays*

Substances

  • Free Radicals
  • Hydroxides
  • Naphthalenes
  • Peroxides
  • Radiation-Sensitizing Agents
  • Spin Labels
  • N,N'-bis(2-hydroxyperoxy-2-methoxyethyl)-1,4,5,8-naphthalenetetracarboxylic diimide
  • Hydroxyl Radical