Biosynthesis and photodynamic efficacy of protoporphyrin IX (PpIX) generated by 5-aminolevulinic acid (ALA) or its hexylester (hALA) in rat bladder carcinoma cells.
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.
Cosserat-Gerardin
I
I
Laboratoire d' Hématologie, Physiologie et Biologie Cellulaire, Faculté de Pharmacie, Nancy, France. cosserat@pharma.u-nancy.fr
Bezdetnaya
L
L
Notter
D
D
Vigneron
C
C
Guillemin
F
F
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D002457:Cell Extracts; D002470:Cell Survival; D003470:Culture Media; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D005453:Fluorescence; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D011524:Protoporphyrins / Q000096:biosynthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D002457:Cell Extracts; D003470:Culture Media; D016895:Culture Media, Serum-Free; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX