ED-110, A NOVEL INDOLOCARBAZOLE, PREVENTS THE GROWTH OF EXPERIMENTAL-TUMORS IN MICE

A new indolocarbazole compound, ED-110, which was obtained by glucosyl ating a microbial product (BE-13793C) and is a potent topoisomerase I inhibitor, showed characteristic inhibitory effects on the growth of 1 2 human tumor cell lines tested. The IC50 values of ED-110 against 9 o f the 12 lines ranged from 11.5 mug/ml to 0.07 mug/ml, while the remai ning 3 lines were quite resistant (IC50, > 100 mug/ml). In in vivo exp eriments, 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 l ife-span of mice bearing P388 leukemia by 25 % was < 2.5 mg/kg/day x 1 0 and the maximum tolerated dose was >160 mg/kg/day x 10. ED-110 was a lso effective against the spontaneous metastasis of mouse Meth A fibro sarcoma cells and the growth of xenografted MKN-45 human stomach cance r cells as well as s.c. implanted mouse colon 26 and IMC carcinoma cel ls. These results indicated that ED-110 may have potential as a new an tineoplastic agent with a large chemotherapeutic index and a wide rang e of effective doses.