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Intracellular Localization is a Cofactor for the Phototoxicity of Protoporphyrin IX in the Gastrointestinal Tract: In Vitro Study ¶ †
Author(s) -
Krieg René C.,
Messmann Helmut,
Schlottmann Klaus,
Endlicher Esther,
Seeger Stephan,
Schölmerich Jürgen,
Knuechel Ruth
Publication year - 2003
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2003)0780393iliacf2.0.co2
Subject(s) - phototoxicity , gastrointestinal tract , protoporphyrin ix , in vitro , intracellular , cofactor , chemistry , biochemistry , photodynamic therapy , enzyme , organic chemistry
Photodynamic therapy (PDT) is a new treatment modality for solid tumors as well as for flat lesions of the gastrointestinal tract. Although the use of 5‐aminolevulinic acid–induced protoporphyrin IX (PPIX) shows important advantages over other photosensitizers, the main mechanisms of phototoxicity induced are still poorly understood. Three human colon carcinoma cell lines with variable degrees of differentiation and a normal colon fibroblast cell line were used to generate a suitable in vitro model for investigation of photosensitizer concentration as well as the applied light dose. Also, the effects of intracellular photosensitizer localization on efficiency of PDT were examined, and cellular parameters after PDT (morphology, mitochondrial transmembrane potential, membrane integrity and DNA fragmentation) were analyzed to distinguish between PDT‐induced apoptosis from necrosis. The fibroblast cell line was less affected by phototoxicity than the tumor cells to a variable degree. Well‐differentiated tumor cells showed higher toxicity than less‐differentiated cells. After irradiation, cell lines with cytosolic or mitochondrial PPIX localization indicate a loss of mitochondrial transmembrane potential resulting in growth arrest, whereas membrane‐bound PPIX induces a loss of membrane integrity and consequent necrosis. Although the absolute amount of intracellular photosensitizer concentration plays the main determining role for PDT efficiency, data indicate that intracellular localization has additional effects on the mode of cell damage.