FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice.
The antitumor activities of FR901228, (E)-(1S,4S,10S,21R)-7-[(Z)- ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23- tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,19,22-pentanone, isolated from Chromobacterium violaceum No. 968, were studied in animals. FR901228 (ip) prolonged the life of mice bearing such murine ascitic tumors as P388 and L1210 leukemias and B16 melanoma, and inhibited (iv) the growth of murine solid tumors (Colon 38 carcinoma, M5076 reticulum cell sarcoma and Meth A fibrosarcoma) and human solid tumors (Lu-65 and LC-6 lung carcinomas, and SC-6 stomach adenocarcinoma) implanted in normal and nude mice, respectively. Its antitumor activity was especially potent against murine Meth A fibrosarcoma and human SC-6 stomach adenocarcinoma which were refractory to mitomycin 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 suggest that FR901228 will be a new type of drug for the treatment of cancer.
Ueda
H
H
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Manda
T
T
Matsumoto
S
S
Mukumoto
S
S
Nishigaki
F
F
Kawamura
I
I
Shimomura
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002861:Chromobacterium; D003110:Colonic Neoplasms / Q000188:drug therapy; D047630:Depsipeptides; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D016685:Mitomycin / Q000494:pharmacology; D009368:Neoplasm Transplantation; D010456:Peptides, Cyclic; D012513:Sarcoma, Experimental / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D010456:Peptides, Cyclic; D016685:Mitomycin; D004317:Doxorubicin; C087123:romidepsin; D005472:Fluorouracil