Modality of cell death induced by Foscan-based photodynamic treatment in human colon adenocarcinoma cell line HT29.
Fiche publication
Date publication
janvier 2004
Journal
Biochemistry. Biokhimiia
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BEZDETNAYA-BOLOTINE Lina
Tous les auteurs :
Marchal S, Bezdetnaya L, Guillemin F
Lien Pubmed
Résumé
Apoptosis induced by photodynamic therapy (PDT) is considered to be an important factor defining the treatment outcome. Nevertheless, the relevance of apoptotic events in overall cell death should be established for every given photosensitizer. The present study addresses the contribution of Foscan-(meta-tetra(hydroxyphenyl)chlorine; mTHPC) photosensitized apoptosis in overall cell death in a model of cultured HT29 adenocarcinoma cells. Early events of cell death were assessed by the evaluation of mitochondrial response to mTHPC-mediated PDT, cytochrome c release and membrane depolarization. Apoptosis was measured through the activity of caspase-3 and the binding of the fluorescent conjugate Ca2+-dependent protein Annexin-V on membrane externalized phosphatidylserine at 2, 4, and 24 h post-PDT. Immediately after mTHPC-PDT, from 28 to 57% cells exhibited cytochrome c release concomitantly with mitochondrial membrane depolarization for light doses inducing more than 90% overall cell death. The maximum of caspase-3 activation (12-fold more than control) was reached 24 h after irradiation at fluence inducing 90% cell death (LD(90)). The corresponding measurement of apoptotic cells (12% of Annexin-V bound cells) confirmed the mild and delayed apoptotic response of HT29 cells to mTHPC-PDT.
Mots clés
Apoptosis, drug effects, Caspase 3, Caspases, metabolism, Colonic Neoplasms, drug therapy, Cytochromes c, metabolism, Endopeptidases, metabolism, HT29 Cells, Humans, Membrane Potentials, drug effects, Mesoporphyrins, pharmacology, Mitochondria, drug effects, Photochemotherapy, Photosensitizing Agents, pharmacology
Référence
Biochemistry Mosc.. 2004 Jan;69(1):45-9