Biosynthesis and photodynamic efficacy of protoporphyrin IX (PpIX) generated by 5-aminolevulinic acid (ALA) or its hexylester (hALA) in rat bladder carcinoma cells.
Fiche publication
Date publication
décembre 2000
Journal
Journal of photochemistry and photobiology. B, Biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BEZDETNAYA-BOLOTINE Lina, Dr VIGNERON Céline
Tous les auteurs :
Cosserat-Gerardin I, Bezdetnaya L, Notter D, Vigneron C, Guillemin F
Lien Pubmed
Résumé
Hexylester of 5-aminolevulinic acid (hALA) has been considered as an alternative to 5-aminolevulinic acid (ALA) for the treatment of malignancies of different origin. The present study addresses the ALA and hALA-induced PpIX pharmacokinetic profile using rat bladder carcinoma cells (AY27). The total PpIX content measured spectrofluorimetrically after extraction procedure at the end of 2 h incubation was at least 1.5-fold greater with hALA compared to ALA despite the difference in concentration of several orders between the two compounds (1 or 5 mM ALA and 5 or 10 x 10(-3) mM hALA). Considerable PpIX efflux was detected in the extracellular medium at the end of the incubation. With 5 mM ALA and 10 x 10(-3) mM hALA, PpIX build-up was continued beyond the incubation period pointing out to enzyme saturation in the biosynthetic pathway or/and the constitution of ALA reserve. Red laser light (lambda=630 nm) irradiation of AY27 cells after 2 h incubation with increasing ALA or hALA concentrations resulted in a nearly equal photocytotoxicity.
Mots clés
Aminolevulinic Acid, pharmacology, Animals, Cell Extracts, Cell Survival, Culture Media, Culture Media, Serum-Free, Dose-Response Relationship, Drug, Fluorescence, Photochemotherapy, methods, Photosensitizing Agents, pharmacokinetics, Protoporphyrins, biosynthesis, Rats, Tumor Cells, Cultured, Urinary Bladder Neoplasms, drug therapy
Référence
J. Photochem. Photobiol. B, Biol.. 2000 Dec;59(1-3):72-9