A photo-activated, protein-based, NO/H2O2 generating system with tumoricidal activity composed of the nitric oxide derivative of apo-metallothionein (thionein-NO) and glucose oxidase.
The S-nitroso derivative of apo-metallothionein (thionein) was prepared by transnitrosation with S-nitrosoglutathione. The thionein-NO thus formed has an absorption maximum at 334 nm. Light-induced NO release from thionein-NO was demonstrated by flash photolysis. This system produces peroxynitrite at neutral pH as evidenced by nitrotyrosine formation. The cytotoxic potential of this protein-based, light-activated NO/H2O2 generating system was demonstrated by exposing human colon adenocarcinoma cells (SW 948) in culture to thionein-NO and glucose oxidase in the presence and absence of light. The cell density of the samples, 72 h subsequent to receiving 1 h of light exposure, decreased by approximately 98%, relative to controls. In comparison, cell density of the samples that were incubated in the presence of catalase and did not receive light treatment, decreased by only approximately 22% after 72 h.
Tannous
M
M
Department of Chemistry and Biochemistry, University of Windsor, Ont., Canada.
Labbe
N
N
Redmond
R W
RW
Mutus
B
B
D005949:Glucose Oxidase / Q000633:toxicity*; D006801:Humans; D006861:Hydrogen Peroxide; D008668:Metallothionein / Q000633:toxicity*; D009569:Nitric Oxide; D017319:Photosensitizing Agents / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D009569:Nitric Oxide; D008668:Metallothionein; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase