FR901228, A NOVEL ANTITUMOR BICYCLIC DEPSIPEPTIDE PRODUCED BY CHROMOBACTERIUM-VIOLACEUM NO-968 .3. ANTITUMOR ACTIVITIES ON EXPERIMENTAL-TUMORS IN MICE

The antitumor activities of FR901228, icyclo[8,7,6]-tricos-16-ene-3,6, 9,19,22-pentanone, isolated from Chromobacterium violaceum No. 968, we re studied in animals. FR901228 (ip) prolonged the life of mice bearin g such murine ascitic tumors as P388 and L1210 leukemias and B16 melan oma, and inhibited (iv) the growth of murine solid tumors (Colon 38 ca rcinoma, M5076 reticulum cell sarcoma and Meth A fibrosarcoma) and hum an solid tumors (Lu-65 and LC-6 lung carcinomas, and SC-6 stomach aden ocarcinoma) implanted in normal and nude mice, respectively. Its antit umor activity was especially potent against murine Meth A fibrosarcoma and human SC-6 stomach adenocarcinoma which were refractory to mitomy cin C or cisplatin. FR901228 also was more effective against mitomycin C-, cyclophosphamide-, vincristine- and 5-fluorouracil-resistant P388 leukemias than against non-resistant P388 in mice. These results sugg est that FR901228 will be a new type of drug for the treatment of canc er.