DNA damage and apoptosis induced by photosensitization of 5,10,15,20-tetrakis (N-methyl-4-pyridyl)-21H,23H-porphyrin via singlet oxygen generation.
Photochem Photobiol
; 85(6): 1391-9, 2009.
Article
en En
| MEDLINE
| ID: mdl-19656322
Cancer photodynamic therapy (PDT) requires photosensitizers that efficiently and selectively destroy tumor cells. We investigated 5,10,15,20-tetrakis (N-methyl-4-pyridyl)-21H,23H-porphyrin (TMPyP) as a potential cancer treatment. Confocal fluorescence microscopy showed that TMPyP was localized in the nuclei, whereas 5-aminolevulinic acid (ALA)-derived protoporphyrin IX (PPIX) was localized diffusely in the cytoplasm of human leukemia (HL-60) cells. In HL-60 cells under UVA irradiation, TMPyP effectively induced apoptosis. Moreover, 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative product of 2'-deoxyguanosine, was accumulated in the DNA of cells treated with photoirradiated TMPyP, whereas only small amounts were observed in ALA-treated cells in the presence of UVA light. TMPyP and UVA caused extensive damage at every guanine residue in DNA fragments obtained from the human p53 tumor suppressor gene and the c-Ha-ras-1 proto-oncogene, whereas PPIX induced little DNA damage under these conditions. Electron spin resonance spectroscopy using a singlet oxygen (1O2) probe and D2O showed that photoexcited TMPyP generated 1O2. These results suggest that photoexcited TMPyP reacts with oxygen to generate 1O2, which in turn, oxidizes guanine residues. Taken together, the results demonstrated that TMPyP was localized in the nucleus where it was photosensitized to induce DNA damage, suggesting that TMPyP may have clinical utility as a nucleus-targeted PDT.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Porfirinas
/
Rayos Ultravioleta
/
Daño del ADN
/
Fármacos Fotosensibilizantes
/
Apoptosis
/
Oxígeno Singlete
Límite:
Humans
Idioma:
En
Revista:
Photochem Photobiol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos