ED-110, a novel indolocarbazole, prevents the growth of experimental tumors in mice.
A new indolocarbazole compound, ED-110, which was obtained by glucosylating a microbial product (BE-13793C) and is a potent topoisomerase I inhibitor, showed characteristic inhibitory effects on the growth of 12 human tumor cell lines tested. The IC50 values of ED-110 against 9 of the 12 lines ranged from 11.5 micrograms/ml to 0.07 microgram/ml, while the remaining 3 lines were quite resistant (IC50, > 100 micrograms/ml). In in vivo experiments, i.p. treatment with ED-110 increased the survival period by more than two-fold in mice implanted i.p. with P388, L1210, L5178Y or EL4 murine leukemic cells. The minimum effective dose increasing the life-span of mice bearing P388 leukemia by 25% was < 2.5 mg/kg/day x 10 and the maximum tolerated dose was > 160 mg/kg/day x 10. ED-110 was also effective against the spontaneous metastasis of mouse Meth A fibrosarcoma cells and the growth of xenografted MKN-45 human stomach cancer cells as well as s.c. implanted mouse colon 26 and IMC carcinoma cells. These results indicated that ED-110 may have potential as a new antineoplastic agent with a large chemotherapeutic index and a wide range of effective doses.
Arakawa
H
H
Banyu Tsukuba Research Institute.
Iguchi
T
T
Yoshinari
T
T
Kojiri
K
K
Suda
H
H
Okura
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology / Q000556:secondary; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002227:Carbazoles; D005960:Glucosides; C078870:ED 110