Photodynamic effects of a novel pterin derivative on a pancreatic cancer cell line.
6-Formylpterin (6FP) has the potential to produce singlet oxygen (1O2) under UV-A radiation. In order to apply this potential to anti-cancer photodynamic therapy (PDT), we prepared a novel variant of 6FP, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one (6FP-tBu-DMF), and examined its photodynamic effects on a pancreatic cancer cell line, Panc-1 cells. The study using laser scanning confocal microscopy showed that the drug uptake, the 1O2 generation, and cell death were observed in the 6FP-tBu-DMF-treated cells, while these phenomena were not observed in the 6FP-treated cells. The MTT assay also showed the decrease in cell viability only in the 6FP-tBu-DMF-treated cells. Since 6FP and 6FP-tBu-DMF generate 1O2 to the same extent under UV-A radiation in aqueous solutions, these results indicated that the differences in the photodynamic effects between 6FP and 6FP-tBu-DMF were entirely attributed to the differences in the cell permeability between them. The development of cell permeable pterin derivatives has the potential for application in PDT.
Yamada
Hiroko
H
Department of Hematology and Oncology, Kyoto University Hospital, Kyoto 606-8507, Japan.
Arai
Toshiyuki
T
Endo
Nobuyuki
N
Yamashita
Kouhei
K
Nonogawa
Mitsuru
M
Makino
Keisuke
K
Fukuda
Kazuhiko
K
Sasada
Masataka
M
Uchiyama
Takashi
T
D045744:Cell Line, Tumor; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D018613:Microscopy, Confocal; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy; D011621:Pteridines / Q000627:therapeutic use*
C504029:2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridin-4-one; D011621:Pteridines