Primary photodamage sites and mitochondrial events after Foscan photosensitization of MCF-7 human breast cancer cells.
To determine the initial photodamage sites of Foscan-mediated photodynamic treatment, we evaluated the enzymatic activities in selected organelles immediately after light exposure of MCF-7 cells. The measurements indicated that the enzymes located in the Golgi apparatus (uridine 5'-diphosphate galactosyl transferase) and in the endoplasmic reticulum (ER) (nicotinamide adenine dinucleotide [reduced] [NADH] cytochrome c [cyt c] reductase) are inactivated by the treatment, whereas mitochondrial marker enzymes (cyt c oxidase and dehydrogenases) were unaffected. This indicates that the ER and the Golgi apparatus are the primary intracellular sites damaged by Foscan-mediated PDT in MCF-7 cells. We further investigated whether the specific mitochondria events could be associated with Foscan photoinduced cell death. The dose response profiles of mitochondrial depolarization and cytochrome c release immediately after Foscan-based PDT were very different from that of overall cell death. By 24 h post-PDT the fluence dependency was strikingly similar for both mitochondrial alterations and cell death. Therefore, although mitochondria are not directly affected by the treatment, they can be strongly implicated in Foscan-mediated MCF-7 cell death by late and indirect mechanism.
Teiten
Marie-Hélène
MH
Unité de Recherche en Thérapie Photodynamique, Centre Alexis Vautrin, Vandoeuvre-les-Nancy Cedex, France.
Marchal
Sophie
S
D'Hallewin
M A
MA
Guillemin
François
F
Bezdetnaya
Lina
L
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005260:Female; D006056:Golgi Apparatus / Q000201:enzymology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008652:Mesoporphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D008928:Mitochondria / Q000201:enzymology / Q000528:radiation effects*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin