Increased DNA repair capacity augments resistance of glioblastoma cells to photodynamic therapy
| Autor: | Agata Ciuba, Maria Wojewódzka, Elżbieta Speina, Konrad Kosicki, Roksana Iwanicka-Nowicka, Anna Fogtman, Marcin Kruszewski, Barbara Tudek, Marta Koblowska, Somayeh Shahmoradi Ghahe, Bartosz Majchrzak |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
DNA Repair
DNA damage DNA repair medicine.medical_treatment Photodynamic therapy Biology medicine.disease_cause Biochemistry 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Humans Cytotoxic T cell Molecular Biology 030304 developmental biology 0303 health sciences Kinase DNA Breaks DNA Neoplasm Cell Biology eye diseases Oxidative Stress Photochemotherapy Drug Resistance Neoplasm Cell culture 030220 oncology & carcinogenesis Cancer cell Cancer research Comet Assay Glioblastoma therapeutics Oxidative stress DNA Damage |
| Zdroj: | DNA Repair. 104:103136 |
| ISSN: | 1568-7864 |
| Popis: | Photodynamic therapy (PDT) is a clinically approved cancer therapy of low invasiveness. The therapeutic procedure involves administering a photosensitizing drug (PS), which is then activated with monochromatic light of a specific wavelength. The photochemical reaction produces highly toxic oxygen species. The development of resistance to PDT in some cancer cells is its main limitation. Several mechanisms are known to be involved in the development of cellular defense against cytotoxic effects of PDT, including activation of antioxidant enzymes, drug efflux pumps, degradation of PS, and overexpression of protein chaperons. Another putative factor that plays an important role in the development of resistance of cancer cells to PDT seems to be DNA repair; however, it has not been well studied so far. To explore the role of DNA repair and other potential novel mechanisms associated with the resistance to PDT in the glioblastoma cells, cells stably resistant to PDT were isolated from PDT sensitive cells following repetitive PDT cycles. Duly characterization of isolated PDT-resistant glioblastoma revealed that the resistance to PDT might be a consequence of several mechanisms, including higher repair efficiency of oxidative DNA damage and repair of DNA breaks. Higher activity of APE1 endonuclease and increased expression and activation of DNA damage kinase ATM was demonstrated in the U-87 MGR cell line, suggesting and proving that they are good targets for sensitization of resistant cells to PDT. |
| Databáze: | OpenAIRE |
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