Lecithinized ascorbic acid (PC-AS) effectively inhibits murine pulmonary metastasis

In order to enhance the lipophilicity and develop the efficacy of ascorbic acid (ASA), we synthesized lecithinized ascorbic acid (PC-AS), in which a l ecithin was covalently bound to ASA. Its pharmacological activity was also evaluated. The IC50 value of scavenge superoxide anions generated from hypo xanthine in combination with xanthine oxidase, indicated that the antioxida tive activity of PC-AS (IC50; 22.19 mu M) was about 60% of that shown by AS A (IC50; 13.35 mu M). Also, PC-AS suppressed in vitro cell growth of Meth A -T, a highly metastatic cell line established by us. Although its potency ( IC50; 110.0 mu M) was a little lower than that of ASA, dramatic suppression was observed under serum-free culture conditions (IC50; 13.0 mu M). In add ition, N-acetylcysteine (NAC), an antioxidant, showed an additive inhibitor y effect on cell growth in combination with PC-AS and ASA. Biodistribution studies revealed that PC-AS persisted longer in the blood (AUC(0-240) min; 182.8 nmole min m(-1)) than ASA (AUC(0-240 min); 79.35 nmole min ml(-1)). I t should be noted that intravenous preadministration of PC-AS significantly and dose-dependently reduced the number of colony formation in an experime ntal murine pulmonary metastasis model. ASA had little effect. [H-3]-labele d Meth A-T cells predominantly accumulated in the lung metastatic target or gan, which was reduced by PC-AS. Our in vivo study showed that PC-AS could not totally prevent pulmonary invasion of Meth A-T:cells, however, PC-AS ef fectively inhibited the number of metastatic colony formation. PC-AS's pote ncy was superior to that of unmodified ASA. These findings might be in part ascribed to changes to lecithinization-induced biodistribution, antioxidat ive activity and cytotoxicity.