HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

DNA damage and apoptosis induced by photosensitization of 5,10,15,20-tetrakis (N-methyl-4-pyridyl)-21H,23H-porphyrin via singlet oxygen generation.

Abstract
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.
AuthorsSaeko Tada-Oikawa, Shinji Oikawa, Junya Hirayama, Kazutaka Hirakawa, Shosuke Kawanishi
JournalPhotochemistry and photobiology (Photochem Photobiol) 2009 Nov-Dec Vol. 85 Issue 6 Pg. 1391-9 ISSN: 1751-1097 [Electronic] United States
PMID19656322 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • MAS1 protein, human
  • Photosensitizing Agents
  • Porphyrins
  • Proto-Oncogene Mas
  • Singlet Oxygen
  • tetra(4-N-methylpyridyl)porphine
Topics
  • Apoptosis (drug effects, radiation effects)
  • Cell Line, Tumor
  • DNA Damage (drug effects, radiation effects)
  • Humans
  • Molecular Structure
  • Photosensitizing Agents (chemistry, pharmacology)
  • Porphyrins (chemistry, pharmacology)
  • Proto-Oncogene Mas
  • Singlet Oxygen (metabolism)
  • Ultraviolet Rays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: