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5-Aminolevulinic acid ester–induced protoporphyrin IX in a murine melanoma cell line

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Abstract

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.

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Abbreviations

5-ALA:

5-Aminolevulinic acid

d-ALA:

Decyl-ALA

h-ALA:

Hexyl-ALA

o-ALA:

Octyl-ALA

B-16:

Murine melanoma cell line

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

Dimethyl sulfoxide

EDTA:

Ethylenediaminetetraacetic acid disodium salt

FCS:

Fetal calf serum

HBSS:

High balanced salt solution

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

TMS:

Tetramethylsilane

PBS:

Phosphate buffer solution

PpIX:

Protoporphyrin IX

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Acknowledgements

We thank the Brazilian agency FAPESP and the program USP-COFECUB (Brazil–France) for financial support. R.F.T. and F.C.B.V. were the recipients of FAPESP fellowships.

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Authors and Affiliations

  1. Departamento de Química, FFCLRP, Universidade de São Paulo, Av. dos Bandeirantes 3900, 14040-901, Ribeirão Preto, São Paulo, Brazil

    Flavia C. B. Vena, Rozane F. Turchiello & Antonio C. Tedesco

  2. LPBC, UMR CNRS 7033 and Université Pierre et Marie Curie, Paris, France

    Isabelle Laville, Sophie Pigaglio & Jocelyne Blais

Authors
  1. Flavia C. B. Vena
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  2. Rozane F. Turchiello
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  3. Isabelle Laville
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  4. Sophie Pigaglio
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  5. Jocelyne Blais
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  6. Antonio C. Tedesco
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Correspondence to Antonio C. Tedesco.

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Vena, F.C.B., Turchiello, R.F., Laville, I. et al. 5-Aminolevulinic acid ester–induced protoporphyrin IX in a murine melanoma cell line. Lasers Med Sci 19, 119–126 (2004). https://doi.org/10.1007/s10103-004-0313-y

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