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Porphyrin accumulation induced by 5-aminolaevulinic acid esters in tumour cells growing in vitro and in vivo.

Tunstall RG, Barnett AA, Schofield J, Griffiths J, Vernon DI, Brown SB, Roberts DJ - Br. J. Cancer (2002)

Bottom Line: Reducing the dose of intravenous hexyl- or benzyl-ALA and topical hexyl-5-aminolaevulinic acid resulted in a dose-dependent reduction in porphyrin accumulation.In contrast to the situation in vivo, all of the 5-aminolaevulinic acid-esters examined were at least as effective as 5-aminolaevulinic acid when applied to cloned CaNT cells in vitro, with the drug concentration required for maximum porphyrin accumulation varying with ester chain-length.These findings suggest that the efficacy of 5-aminolaevulinic esters may vary depending on the esterase activity of the target tissue, and suggest caution when interpreting the findings of in vitro studies using these and similar prodrugs.

View Article: PubMed Central - PubMed

Affiliation: Centre for Photobiology and Photodynamic Therapy, University of Leeds, Leeds LS2 9JT, UK.

ABSTRACT
The ability of 5-aminolaevulinic acid and some of its esterified derivatives to induce porphyrin accumulation has been examined in CaNT murine mammary carcinoma cells growing in culture and as tumours in vivo. Topical or intravenous administration of 5-aminolaevulinic acid-esters to mice bearing subcutaneous tumours produced lower porphyrin levels in the tumour than an equimolar dose of 5-aminolaevulinic acid. Reducing the dose of intravenous hexyl- or benzyl-ALA and topical hexyl-5-aminolaevulinic acid resulted in a dose-dependent reduction in porphyrin accumulation. A number of normal tissues accumulated higher concentrations of porphyrins than tumour tissue following intravenous administration of 5-aminolaevulinic acid-esters. Esterase activity in these normal tissues was greater than that in tumour tissue. In contrast to the situation in vivo, all of the 5-aminolaevulinic acid-esters examined were at least as effective as 5-aminolaevulinic acid when applied to cloned CaNT cells in vitro, with the drug concentration required for maximum porphyrin accumulation varying with ester chain-length. Tumour cells growing in culture released esterase activity into the medium. These findings suggest that the efficacy of 5-aminolaevulinic esters may vary depending on the esterase activity of the target tissue, and suggest caution when interpreting the findings of in vitro studies using these and similar prodrugs.

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Porphyrin concentration in cultured CaNT cells after 3 h incubation in serum-free medium containing ALA or (A) elthyl-, propyl- or butyl-ester (B) pentyl-, hexyl-, cyclohexyl- or benzyl-ester. Data are means±s.e. (n=8).
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fig4: Porphyrin concentration in cultured CaNT cells after 3 h incubation in serum-free medium containing ALA or (A) elthyl-, propyl- or butyl-ester (B) pentyl-, hexyl-, cyclohexyl- or benzyl-ester. Data are means±s.e. (n=8).

Mentions: All ALA-esters induced intracellular accumulation of porphyrins in tumour cell clones (Figure 4a,bFigure 4


Porphyrin accumulation induced by 5-aminolaevulinic acid esters in tumour cells growing in vitro and in vivo.

Tunstall RG, Barnett AA, Schofield J, Griffiths J, Vernon DI, Brown SB, Roberts DJ - Br. J. Cancer (2002)

Porphyrin concentration in cultured CaNT cells after 3 h incubation in serum-free medium containing ALA or (A) elthyl-, propyl- or butyl-ester (B) pentyl-, hexyl-, cyclohexyl- or benzyl-ester. Data are means±s.e. (n=8).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376104&req=5

fig4: Porphyrin concentration in cultured CaNT cells after 3 h incubation in serum-free medium containing ALA or (A) elthyl-, propyl- or butyl-ester (B) pentyl-, hexyl-, cyclohexyl- or benzyl-ester. Data are means±s.e. (n=8).
Mentions: All ALA-esters induced intracellular accumulation of porphyrins in tumour cell clones (Figure 4a,bFigure 4

Bottom Line: Reducing the dose of intravenous hexyl- or benzyl-ALA and topical hexyl-5-aminolaevulinic acid resulted in a dose-dependent reduction in porphyrin accumulation.In contrast to the situation in vivo, all of the 5-aminolaevulinic acid-esters examined were at least as effective as 5-aminolaevulinic acid when applied to cloned CaNT cells in vitro, with the drug concentration required for maximum porphyrin accumulation varying with ester chain-length.These findings suggest that the efficacy of 5-aminolaevulinic esters may vary depending on the esterase activity of the target tissue, and suggest caution when interpreting the findings of in vitro studies using these and similar prodrugs.

View Article: PubMed Central - PubMed

Affiliation: Centre for Photobiology and Photodynamic Therapy, University of Leeds, Leeds LS2 9JT, UK.

ABSTRACT
The ability of 5-aminolaevulinic acid and some of its esterified derivatives to induce porphyrin accumulation has been examined in CaNT murine mammary carcinoma cells growing in culture and as tumours in vivo. Topical or intravenous administration of 5-aminolaevulinic acid-esters to mice bearing subcutaneous tumours produced lower porphyrin levels in the tumour than an equimolar dose of 5-aminolaevulinic acid. Reducing the dose of intravenous hexyl- or benzyl-ALA and topical hexyl-5-aminolaevulinic acid resulted in a dose-dependent reduction in porphyrin accumulation. A number of normal tissues accumulated higher concentrations of porphyrins than tumour tissue following intravenous administration of 5-aminolaevulinic acid-esters. Esterase activity in these normal tissues was greater than that in tumour tissue. In contrast to the situation in vivo, all of the 5-aminolaevulinic acid-esters examined were at least as effective as 5-aminolaevulinic acid when applied to cloned CaNT cells in vitro, with the drug concentration required for maximum porphyrin accumulation varying with ester chain-length. Tumour cells growing in culture released esterase activity into the medium. These findings suggest that the efficacy of 5-aminolaevulinic esters may vary depending on the esterase activity of the target tissue, and suggest caution when interpreting the findings of in vitro studies using these and similar prodrugs.

Show MeSH
Related in: MedlinePlus