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1 November 2001 The Effects of 5-Aminolevulinic Acid Esters on Protoporphyrin IX Production in Human Adenocarcinoma Cell Lines
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Abstract
Photodynamic diagnosis (PDD) and photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)–induced protoporphyrin IX (PPIX) is an interesting approach to detect and treat dysplasia and early cancers in the gastrointestinal tract. Because of low lipophilicity resulting in poor penetration across cell membranes, high doses of ALA should be administered in order to reach clinically relevant levels of PPIX. One way of increasing PPIX accumulation is derivatization of ALA into a more lipophilic molecule. In our in vitro study, different esterifications of ALA were investigated to analyze the effects on PPIX accumulation in human adenocarcinoma cell lines. For systematic analysis of cell type–specific PPIX accumulation, three human adenocarcinoma cell lines (SW480, HT29 and CaCo2) and a fibroblast cell line (CCD18) were tested. 3-(4,5-Dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assays were performed to ensure that the ALA esters showed no cellular dark toxicity. Different concentrations (ranging from 0.012 to 0.6 mmol/L, 3 h) and incubation times (5, 10, 30, 180 min; 0.12 mmol/L) were examined. PPIX accumulation was measured using flow cytometry. ALA esters, especially ALA-hexylester and ALA-benzylester, induced significant higher PPIX levels in adenocarcinoma cell lines when compared with ALA and may be promising candidates for PDT and PDD.
H. Brunner, F. Hausmann, R. C. Krieg, E. Endlicher, J. Schölmerich, R. Knuechel and H. Messmann "The Effects of 5-Aminolevulinic Acid Esters on Protoporphyrin IX Production in Human Adenocarcinoma Cell Lines ," Photochemistry and Photobiology 74(5), (1 November 2001). https://doi.org/10.1562/0031-8655(2001)074<0721:TEOAAE>2.0.CO;2
Received: 3 May 2001; Accepted: 1 August 2001; Published: 1 November 2001
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