Ibuprofen and ketoprofen potentiate UVA-induced cell death by a photosensitization process.
Fiche publication
Date publication
août 2017
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GRANDEMANGE Stéphanie
Tous les auteurs :
Bignon E, Marazzi M, Besancenot V, Gattuso H, Drouot G, Morell C, Eriksson LA, Grandemange S, Dumont E, Monari A
Lien Pubmed
Résumé
Nonsteroidal 2-arylproprionic acids are widely used, over-the-counter, anti-inflammatory drugs. Photosensitivity is a commonly overlooked adverse effect of these drugs. Based on the combined use of cell viability assays and molecular modeling, we prove and rationalize the photochemical pathways triggering photosensitization for two drugs, ibuprofen and ketoprofen. As its parent compound benzophenone, ketoprofen produces singlet oxygen, upon triplet manifold population. However, ibuprofen and ketoprofen photodissociate and hence may generate two highly reactive radicals. The formation of metastable aggregates between the two drugs and B-DNA is also directly probed by molecular dynamics. Our approach characterizes the coupled influence of the drug's intrinsic photochemistry and the interaction pattern with DNA. The photosensitization activity of nonsteroidal 2-arylproprionic acids, being added to gels and creams for topical use, should be crucially analyzed and rationalized to enact the proper preventive measures.
Mots clés
Apoptosis, drug effects, Cell Death, drug effects, Cell Line, Tumor, Cell Survival, drug effects, Drug Synergism, Humans, Ibuprofen, chemistry, Ketoprofen, chemistry, Models, Molecular, Molecular Structure, Photosensitizing Agents, chemistry, Structure-Activity Relationship, Ultraviolet Rays, adverse effects
Référence
Sci Rep. 2017 Aug 21;7(1):8885