Antitumor activity and toxicity in mice of RA-700, a cyclic hexapeptide

The antitumor activity of RA-700, a cyclic hexapeptide isolated from Rubia Cordifolia, was evaluated in comparison with deoxy-bouvardin and vincristine (VCR). As regards the proliferation of L1210 cultured cells, the cytotoxicity of RA-700 was similar to that of VCR but superior to that of deoxy-bouvardin. The IC50 value of RA-700 was 0.05 mcg/ml under our experimental conditions. RA-700 inhibited the incorporation of 14C-leucine at a concentration at which no effects were observed on the incorporation of 3H-thymidine and 3H-uridine in L1210 culture cells in vitro. The antitumor activity of RA-700 was similar to that of deoxy-bouvardin and VCR against P388 leukemia. Daily treatment with RA-700 at an optimal dose resulted in 118% ILS. As with deoxy-bouvardin and VCR, the therapeutic efficacy of RA-700 depends on the time schedule. RA-700 showed marginal activity against L1210 leukemia (50% ILS), similar to that of deoxy-bouvardin but inferior to that of VCR. RA-700 inhibited Lewis tumor growth in the early stage after tumor implantation, whereas deoxy-bouvardin and VCR did not. As regards toxicity, a slight reduction of peripheral WBC counts was observed with the drug, but no reduction of RBC and platelet counts. BUN, creatinine, GPT and GOT levels in plasma did not change with the administration of the drug.