5-aminolevulinic acid ester-induced protoporphyrin IX in a murine melanoma cell line.
The use of 5-aminolevulinic acid (5-ALA) ester derivatives as precursors of endogenous protoporphyrin IX (PpIX) has been proposed as a good strategy for improved drug diffusion across biological membranes. In the present work, the 5-ALA ester derivatives hexyl-ALA (h-ALA), octyl-ALA (o-ALA), and decyl-ALA (d-ALA) were synthesized, and their efficacy to induce endogenous PpIX was explored in a murine melanoma cell line (B-16) as compared with that of 5-ALA. The maximum level of PpIX induced in cells treated with 5-ALA, h-ALA, o-ALA, and d-ALA was reached at optimal concentrations of 0.3, 0.075, 0.1, and 0.075 mM, respectively. The derivatives h-ALA and o-ALA appear as the most efficient PpIX precursors in this cell line, since a higher or similar PpIX production could be achieved with a fourfold and threefold lower dose of these precursors compared with 5-ALA. The phototoxicity effect of h-ALA and o-ALA ester derivatives showed the same phototoxicity behavior detected for 5-ALA but at much lower drug doses. Our study suggests that h-ALA and o-ALA esters improve intracellular PpIX formation in B-16 cells at reduced concentrations. This should enable clinical applications at lower precursor doses with reduced effective costs.
Vena
Flavia C B
FC
Departamento de Química, FFCLRP, Universidade de São Paulo, Av. dos Bandeirantes 3900, 14040-901 Ribeirão Preto, São Paulo, Brazil.
Turchiello
Rozane F
RF
Laville
Isabelle
I
Pigaglio
Sophie
S
Blais
Jocelyne
J
Tedesco
Antonio C
AC
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011524:Protoporphyrins / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX