Effect of lecithinized superoxide dismutase (PC-SOD) on experimental pulmonary metastasis in mice.
The inhibitory effect of lecithinized superoxide dismutase (PC-SOD) on pulmonary metastasis in mice was investigated. In an experimental pulmonary metastasis model employing Meth A-T cells, significant and dose-dependent inhibition was observed after i.v. pre-administration of PC-SOD. Unmodified SOD (U-SOD) was also effective, but a 10-times higher dose was necessary to be significant. The pulmonary accumulation of Meth A-T cells labeled with 5-[125I]iodo-2'-deoxyuridine was not reduced by either PC-SOD or U-SOD, and neither of the compounds decreased pulmonary MPO activity. However, PC-SOD increased pulmonary SOD activity for longer, compared with U-SOD. In vitro addition of PC-SOD dose-dependently suppressed the growth of Meth A-T cells, while U-SOD had little effect. The combination of PC-SOD and S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a nitric oxide (NO)-generating agent, had an additive effect. It was also found that PC-SOD prevented a decrease of pulmonary NOx level following tumor cell inoculation. It was concluded that PC-SOD possessed antimetastatic activity, and its potency was superior to that of U-SOD. These results suggest that PC-SOD may prevent the excessive formation of oxygen radicals and peroxynitrite (ONOO-) which cause cell damage and facilitate tumor metastasis.
Takenaga
M
M
The Second Department of the Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
Igarashi
R
R
Ochiai
A
A
Mizushima
Y
Y
D000818:Animals; D004357:Drug Synergism; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008175:Lung Neoplasms / Q000201:enzymology / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000008:administration & dosage; D010396:Penicillamine / Q000008:administration & dosage / Q000031:analogs & derivatives; D009195:Peroxidase / Q000378:metabolism; D010713:Phosphatidylcholines; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D005609:Free Radicals; D020030:Nitric Oxide Donors; D010713:Phosphatidylcholines; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D009195:Peroxidase; D013482:Superoxide Dismutase; D010396:Penicillamine