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.