ED-110, a Novel Indolocarbazole, Prevents the Growth of Experimental Tumors in Mice

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Abstract
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 μg/ml to 0.07 μg/ml, while the remaining 3 lines were quite resistant (IC50, >100μg/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 160 mg/kg/day × 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.