DNA Damage and Apoptosis Induced by Photosensitization of 5,10,15,20‐Tetrakis (N‐methyl‐4‐pyridyl)‐21 H,23 H‐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)‐21 H,23 H‐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 p 53 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 (1 O 2) probe and D 2 O showed that photoexcited TMPyP generated 1 O 2. These results suggest that photoexcited TMPyP reacts with oxygen to generate 1 O 2, 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.
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Cationic 5,10,15,20-tetrakis(N-methyl-4-pyridyl)-21H,23H-porphyrin localizes mostly in nuclei of human leukemia HL-60 cells and UVA sensitizes formation of 8-oxoGua through predominant Type II mechanisms.
“Cationic 5,10,15,20-tetrakis (N-methyl-4-pyridyl)-21H,23H-porphyrin that is mostly localized in the nuclei of human leukemia HL-60 cells as inferred from confocal fluorescence microscopy is able to UVA sensitize the formation of 8-oxoGua through predominant Type II photosensitization mechanisms (186).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [186]
Protoporphyrin IX derived from 5-aminolevulinic acid localizes preferentially in cytoplasm and generates only small amounts of 8-oxoGua upon UVA illumination.
“In contrast, protoporphyrin IX derived from 5-aminolevulinic acid and whose preferential localization was observed in the cytoplasm was found to generate only small amounts of 8-oxoGua upon UVA illumination (186).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [186]
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Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup>
Cadet, J., Mouret, S., Ravanat, J., & Douki, T. (2012) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2012.01200.x · Cited by 300 · see citing works
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- Authors
- Tada‐Oikawa, S., Oikawa, S., Hirayama, J., Hirakawa, K., & Kawanishi, S.
- Affiliations
- Mie University (JP)
- Shizuoka University (JP)
- Suzuka University of Medical Science (JP)
- Corresponding author
- Kawanishi, Shosuke
- Venue
- Photochemistry and Photobiology
- Publisher
- Wiley
- Published
- 2009-10-22
- Volume
- 85
- Issue
- 6
- Pages
- 1391-1399
- ISSN
- 0031-8655 (ISSN-L)
- 1751-1097
- OpenAlex
- W2021861087
- Cited by
- 80
- References
- 52
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 7 · 2016: 6 · 2015: 5 · 2014: 7 · 2013: 4 · 2012: 8
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Photochemistry and Photobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (21390195)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Physical Sciences › Materials Science › Materials Chemistry › Porphyrin and Phthalocyanine Chemistry
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- TMPyP, photosensitizers, photodynamic therapy, singlet oxygen, DNA damage, apoptosis, guanine oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine, protoporphyrin IX, 5-aminolevulinic acid, UVA irradiation, HL-60 cells, p53, c-Ha-ras-1, nuclear targeting
- MeSH terms
- Proto-Oncogene Mas, DNA Damage, Humans, Porphyrins, Ultraviolet Rays, Molecular Structure, Apoptosis, Photosensitizing Agents, Singlet Oxygen, Cell Line, Tumor
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