Metabolic characterization of tumor cell-specific protoporphyrin IX accumulation after exposure to 5-aminolevulinic acid in human colonic cells

Krieg, René C. and Messmann, Helmut and Rauch, Joachim and Seeger, Stefan and Knuechel, Ruth (2002) Metabolic characterization of tumor cell-specific protoporphyrin IX accumulation after exposure to 5-aminolevulinic acid in human colonic cells. PHOTOCHEMISTRY AND PHOTOBIOLOGY, 76 (5). pp. 518-525. ISSN 0031-8655, 1751-1097

Full text not available from this repository. (Request a copy)

Abstract

5-Aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) fluorescence has been shown to have high tumor cell selectivity in various organs, including the gastrointestinal (GI) tract. To better understand and to possibly find new approaches to therapeutic application, we investigated the uptake kinetics and consequent metabolism of ALA and PPIX, respectively. Three colon carcinoma (CaCo2, HT29, SW480) and a stromal cell line (fibroblast, CCD18) were chosen to mimic important aspects of malignant mucosa of the GI tract. Because differential PPIX concentrations in these cell lines represented the in vivo observations (ratio tumor vs normal 10:1-20:1), we analyzed the ALA uptake, mitochondrial properties and key molecules of PPIX metabolism (porphobilinogen deaminase [PBGD], ferrochelatase [FC], iron content, transferrin receptor content). The tumor-preferential PPIX accumulation is strongly influenced, but not solely determined, by activity differences between the PPIX-producing PBGD and the PPIX-converting FC, when compared with fibroblasts. Tumor-specific PPIX accumulation is generated by ALA conversion rather than by initial ALA uptake because no significant overall difference in uptake (about 0.6 mug ALA/mg protein) of ALA is seen. In conclusion, further research of tumor cell selectivity of PPIX fluorescence should focus on the mechanisms responsible for an altered PPIX metabolism to find tumor-specific target molecules, thus leading to an improved clinical practicability of ALA application and consequent endoscopy.

Item Type: Article
Uncontrolled Keywords: DELTA-AMINOLEVULINIC-ACID; HUMAN BLADDER-CARCINOMA; HIGH-GRADE DYSPLASIA; PHOTODYNAMIC THERAPY; IN-VITRO; BARRETTS-ESOPHAGUS; PORPHOBILINOGEN DEAMINASE; PORPHYRIN BIOSYNTHESIS; FLUORESCENCE DETECTION; ADENOCARCINOMA CELLS;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 27 Aug 2021 04:41
Last Modified: 27 Aug 2021 04:41
URI: https://pred.uni-regensburg.de/id/eprint/39752

Actions (login required)

View Item View Item