Effect of lecithinized superoxide dismutase (PC-SOD) on experimental pulmonary metastasis in mice

The inhibitory effect of lecithinized superoxide dismutase (PC-SOD) on pulm onary metastasis in mice was investigated. In an experimental pulmonary met astasis model employing Meth A-T cells, significant and dose-dependent inhi bition 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-[ I-125]iodo-2'-deoxyuridine was not reduced by either PC-SOD or U-SOD, and n either of the compounds decreased pulmonary MPO activity. However, PC SOD i ncreased pulmonary SOD activity for longer, compared with U-SOD. In vitro a ddition 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-a cetyl-D,L-penicillamine (SNAP), a nitric oxide (NO)-generating agent, had a n additive effect. It was also found that PC-SOD prevented a decrease of pu lmonary NOx level following tumor cell inoculation. It was concluded that P C-SOD possessed antimetastatic activity, and its potency was superior to th at of U-SOD. These results suggest that PC-SOD may prevent the excessive fo rmation of oxygen radicals and peroxynitrite (ONOO-) which cause cell damag e and facilitate tumor metastasis. (C) 1998 Elsevier Science Inc.