Flavoprotein miniSOG as a genetically encoded photosensitizer for cancer cells
| Autor: | Sergey Lukyanov, Natalia V. Klementieva, Boris E. Shakhov, Nadezhda I. Ignatova, Elena V. Zagaynova, Marina V. Shirmanova, Ludmila B. Snopova, Alina P. Ryumina, Ilya V. Turchin, Arkady F. Fradkov, Maria M. Kuznetsova, Konstantin A. Lukyanov, Ekaterina O. Serebrovskaya |
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| Rok vydání: | 2013 |
| Předmět: |
DNA Repair
Light DNA damage DNA repair Riboflavin Biophysics Mice Nude Biology Biochemistry Cell Line HeLa Mice Cell Line Tumor Animals Humans Molecular Biology Photosensitizing Agents Cell Death Flavoproteins Caspase 3 Cell Membrane HEK 293 cells Genetic Therapy biology.organism_classification Xenograft Model Antitumor Assays Molecular biology Chromatin Mitochondria Cell biology Oxygen HEK293 Cells Cell culture Cancer cell Female Phototoxicity DNA Damage Dermatitis Phototoxic HeLa Cells |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - General Subjects. 1830:5059-5067 |
| ISSN: | 0304-4165 |
| DOI: | 10.1016/j.bbagen.2013.07.015 |
| Popis: | Background Genetically encoded photosensitizers are a promising optogenetic instrument for light-induced production of reactive oxygen species in desired locations within cells in vitro or whole body in vivo. Only two such photosensitizers are currently known, GFP-like protein KillerRed and FMN-binding protein miniSOG. In this work we studied phototoxic effects of miniSOG in cancer cells. Methods HeLa Kyoto cell lines stably expressing miniSOG in different localizations, namely, plasma membrane, mitochondria or chromatin (fused with histone H2B) were created. Phototoxicity of miniSOG was tested on the cells in vitro and tumor xenografts in vivo. Results Blue light induced pronounced cell death in all three cell lines in a dose-dependent manner. Caspase 3 activation was characteristic of illuminated cells with mitochondria- and chromatin-localized miniSOG, but not with miniSOG in the plasma membrane. In addition, H2B-miniSOG-expressing cells demonstrated light-induced activation of DNA repair machinery, which indicates massive damage of genomic DNA. In contrast to these in vitro data, no detectable phototoxicity was observed on tumor xenografts with HeLa Kyoto cell lines expressing mitochondria- or chromatin-localized miniSOG. Conclusions miniSOG is an excellent genetically encoded photosensitizer for mammalian cells in vitro, but it is inferior to KillerRed in the HeLa tumor. General significance This is the first study to assess phototoxicity of miniSOG in cancer cells. The results suggest an effective ontogenetic tool and may be of interest for molecular and cell biology and biomedical applications. |
| Databáze: | OpenAIRE |
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