Messmann, H and Geisler, M and Gross, U and Abels, C and Szeimies, RM and Steinbach, P and Knuchel, R and Doss, M and Scholmerich, J and Holstege, A (1997) Influence of a haematoporphyrin derivative on the protoporphyrin IX synthesis and photodynamic effect after 5-aminolaevulinic acid sensitization in human colon carcinoma cells. BRITISH JOURNAL OF CANCER, 76 (7). pp. 878-883. ISSN 0007-0920,
Full text not available from this repository.Abstract
Haematoporphyrin derivatives (HPDs) are potent sensitizers in photodynamic therapy (PDT), associated with prolonged skin photosensitivity. 5-Aminolaevulinic acid (5-ALA), a natural precusor of haem, is converted intracellularly into the photosensitive agent protoporphyrin IX (PPIX), causing direct cytotoxicity after laser light irradiation but limited skin photosensitivity over 1-2 days and higher tumour selectivity. Unfortunately, the use of 5-ALA in PDT has been shown to cause only superficial tissue necrosis. Therefore, a combination of HPD and 5-ALA could be of great clinical value in the treatment of tumours if a synergistic effect of both sensitizers on tumour cell necrosis with less skin photosensitivity could be demonstrated. Human colon adenocarcinoma cells (HT-29) were cultured with either HPD or 5-ALA alone, simultaneously for 24 h with 5-ALA and HPD or in succession with 5-ALA (18 h) followed by HPD (6 h at different concentrations. Intracellular PPIX concentrations were determined by high-performance thin-layer chromatography. Furthermore, PDT was performed with an incoherent light source (lambda = 580-740 nm) using a light dose of 30 J cm(-2) and an output power of 40 mW cm(-2). The intracellular PPIX concentration correlated well with 5-ALA drug dose and incubation time and was highest after single 5-ALA sensitization. In the presence of HPD, either simultaneously or sequentially, PPIX decreased significantly. The PDT effect after simultaneous incubation with both sensitizers for 24 h was not superior to incubation with HPD alone. If 5-ALA incubation (18 h) was followed by HPD (6 h) cytotoxicity after PDT was higher than with either single drug. 5-ALA (80 mu g ml(-1)) led to a decrease in tumour cell viability by 40%. A similar effect could be observed when 5-ALA and HPD were sequentially combined allowing for a reduction of the 5-ALA dose from 80 mu g ml(-1) in the absence of HPD to 60 mu g ml(-1) and 5 mu g ml(-1) together with 0.5 mu g ml(-1) and 2 mu g ml(-1) HPD respectively. We speculate that the enhanced PDT effect after the combined administration of 5-ALA and HPD to cultures of colon carcinoma cells should be even more impressive in the tumour in vivo, since HPD primarily targets the tumour microvasculature and secondarily tumour cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 5-AMINOLEVULINIC ACID; MURINE TUMOR; THERAPY; HEMATOPORPHYRIN; PHOTOSENSITIZATION; DESTRUCTION; ENHANCEMENT; CANCER; LIGHT; photodynamic therapy; sensitizer combination; 5-aminolaevulinic acid; haematoporphyrin derivatives |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:33 |
| URI: | https://pred.uni-regensburg.de/id/eprint/51126 |
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