A novel antitumor cyclic hexapeptide (RA-700) obtained from Rubiae radix.
The antitumor activity of a newly obtained cyclic hexapeptide, RA-700, from Rubiae Radix was studied using several murine experimental tumor systems. In P388 leukemia (inoculated intraperitoneally (i.p.), administered i.p.: i.p.-i.p.) the maximal increase in life span (ILSmax) resulting from an administration of RA-700 (4 mg/kg/d for 9 d) was 134% and the therapeutic ratio was 400. These values indicate that RA-700 has higher anti-tumor activity and broader active dose range than that of mitomycin C (MMC, 1 mg/kg/d for 9 d) which was used as a positive control. In the study of the treatment schedules on P388, RA-700 had the highest activity by consecutive injections. In MOPC-104E mouse plasmacytoma system (i.p.-i.p.), ILSmax of RA-700 (2.5 mg/kg/d for 9 d) was 84%. In a solid tumor, colon adenocarcinoma 38 (subcutaneously (s.c.)-intravenously (i.v.], RA-700 (4 mg/kg/d for 11 d) showed complete cures (8/8) compared to MMC (0.5 mg/kg/d for 11 d) which showed one cure out of 8 animals. In the study of a model of the inhibition of lymph node metastasis using P388 leukemia, the administration of RA-700 at more than 2.5 mg/kg/d i.v. for 7 d resulted in the survival of all animals (5/5) for over 60 d. In the amputation system of the same metastasis model at a dose of 4 mg/kg/d i.v. for 7 d, 3 animals out of 5 survived over 60 d.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000633:toxicity; D004317:Doxorubicin / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005260:Female; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D016685:Mitomycin; D008937:Mitomycins / Q000627:therapeutic use; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010456:Peptides, Cyclic / Q000494:pharmacology* / Q000633:toxicity; D010946:Plants, Medicinal / Q000032:analysis*
D000972:Antineoplastic Agents, Phytogenic; D008937:Mitomycins; D010456:Peptides, Cyclic; D016685:Mitomycin; D004317:Doxorubicin; C043548:RA VII