The synthetic hepatic peptides pyroglutamylglutamylglycylserylasparagine and pyroglutamylglutamylglycylserylaspartic acid inhibit growth of MH1C1 rat hepatoma cells transplanted into Buffalo rats or athymic mice.

Repeated i.p. injections of the synthetic peptides pyroglutamylglutamylglycylserylasparagine and pyroglutamylglutamylglycylserylaspartic acid inhibited the long-term growth of MH1C1 rat hepatoma cells by 50-70% in three in vivo models: metastatic colony growth in the lungs of young Buffalo rats; s.c. tumor growth in young Buffalo rats; and s.c. tumor growth in athymic mice. The amide free peptide pyroglutamylglutamylglycylserylaspartic acid which inhibited the tumor growth in all the models showed a curvilinear dose-response relationship with a maximal effect at 1000 pmol/animal in mice and at 100 pmol/animal in rats. The amidated peptide pyroglutamylglutamylglycylserylasparagine, which was only tested in the lung model, showed growth inhibition with 2, 20, or 200 pmol/animal, but 200 pmol/animal was most effective. We have recently reported that these peptides show cochromatography with hepatic growth inhibitory peptides, isolated from mouse liver.