Iminium salt of copper benzochlorin (CDS1), a novel photosensitizer for photodynamic therapy: mechanism of cell killing.
The mechanism of cell killing by CDS1, an iminium salt of octaethylbenzochlorin with copper in the aromatic ring, in combination with light from a noncoherent light source was investigated. Using a standard clonogenic assay and the AY-27 FANFT tumor line, photoactivation of CDS1 was shown to be cytotoxic. The photodynamic cell killing ability of CDS1 required the presence of molecular oxygen. The reactive species generated by light activation of CDS1 were effectively quenched by N,N'-diphenyl-p-phenylenediamine. Additionally, the photodynamic effect of CDS1 was not enhanced by deuterium oxide. To characterize the reactive oxygen species generated by the photoactivation of CDS1 the well-characterized erythrocyte ghost model was used. Superoxide dismutase and catalase were potent inhibitors of CDS1-induced lipid peroxidation of erythrocyte membranes. Sodium azide only partially inhibited lipid peroxidation. These findings differed from the known singlet oxygen generator, tin (II) etiopurpurin dichloride (SnET2). Sodium azide was a potent inhibitor of SnET2-induced lipid peroxidation, whereas superoxide dismutase and catalase were totally ineffective. Based on these results, we conclude that CDS1 requires the presence of molecular oxygen for cell killing to occur but appears to act primarily through a non-singlet oxygen mechanism.
Hampton
J A
JA
Department of Urology, Medical College of Ohio, Toledo 43699.
Skalkos
D
D
Taylor
P M
PM
Selman
S H
SH
D000818:Animals; D016923:Cell Death / Q000187:drug effects* / Q000528:radiation effects; D003905:Deuteroporphyrins / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007097:Imines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008027:Light; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D003905:Deuteroporphyrins; D007097:Imines; D017319:Photosensitizing Agents; C081504:copper benzochlorin