title: Apoptotic and autophagic responses to photodynamic therapy in 1c1c7 murine hepatoma cells.
abstract: Photodynamic therapy (PDT) is a process that can induce apoptosis, autophagy or both depending on the cell phenotype. Apoptosis is a pathway to cell death while autophagy can protect from photokilling or act as a death pathway. In a previous study, we reported a cytoprotective effect of autophagy in murine leukemia cell lines where both autophagy and apoptosis occur within minutes after irradiation of photosensitized cells. In this study, we examined the effects of mitochondrial photodamage catalyzed by low (≤ 1 μM) concentrations of the photosensitizing agent termed benzoporphyrin derivative (BPD, Verteporfin) on murine hepatoma 1c1c7 cells. Apoptosis was not observed until several hours after irradiation of photosensitized cells. Autophagy was clearly cytoprotective since PDT efficacy was significantly enhanced in a knockdown sub-line (KD) in which the level of a critical autophagy protein (Atg7) was markedly reduced. This result indicates that autophagy can protect from phototoxicity even when apoptosis is substantially delayed. Much higher concentrations (≥ 10 μM) of BPD had previously been shown to inhibit autophagosome formation. Phototoxicity studies performed with 10 μM BPD and a proportionally reduced light dose were consistent with the absence of an autophagic process in wild-type (WT) cells under these conditions.
authors.affiliation: Department of Biology, University of Detroit Mercy, Detroit, MI, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Andrzejak
authors.forename: Michael
authors.initials: M
authors.lastname: Price
authors.forename: David H
authors.initials: DH
authors.lastname: Kessel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001343:Autophagy / Q000187:drug effects / Q000528:radiation effects; D000071193:Autophagy-Related Protein 7; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology* / Q000648:ultrastructure; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D017484:Dermatitis, Phototoxic; D004305:Dose-Response Relationship, Drug; D055785:Gene Knockdown Techniques; D007938:Leukemia / Q000473:pathology; D008027:Light; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use; D011166:Porphyrins / Q000494:pharmacology / Q000627:therapeutic use; D014617:Vacuoles / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D000077362:Verteporfin
chemical_list: C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D000071193:Autophagy-Related Protein 7