Antitumor effect of kazusamycin B on experimental tumors.
Kazusamycin B, a novel antibiotic (MW 542) isolated from fermentation broth of Streptomyces sp. No. 81-484 showed a broad antitumor spectrum both in vitro and in vivo. IC50 against the growth of tumor cells was around 1 ng/ml at 72 hours-exposure in vitro. Intraperitoneal injection of the antibiotic was effective in inhibiting the growth of murine tumors, S180, P388, EL-4, and B16. It was also active against doxorubicin-resistant P388, hepatic metastases of L5178Y-ML, pulmonary metastases of 3LL, and human mammary cancer MX-1 xenografted to nude mice. However, the activity of kazusamycin B toward L1210 or human lung cancer LX-1 was weaker. According to the results of comparative studies on the effect of kazusamycins B and A, an analog of B, there seemed to be no significant difference in their effectiveness. The effective dose range and toxicity were markedly dependent on tumor lines tested and the regimen used. Maximum tolerated dose in mice with subcutaneous tumors was much higher than that in mice bearing ascitic leukemia as P388. Although intermittent administration could greatly reduce the cumulative toxicity of the drug, therapeutic effect was similar with both successive and intermittent administration schedules.
Exploratory Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
E
E
Yoshida
K
K
Komiyama
K
K
Naito
Y
Y
Watanabe
K
K
Takamiya
A
A
Okura
K
K
Funaishi
K
K
Kawamura
S
S
Funayama
I
I
Umezawa
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D005231:Fatty Acids, Unsaturated / Q000627:therapeutic use; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009374:Neoplasms, Experimental / Q000188:drug therapy*
D005231:Fatty Acids, Unsaturated; C051484:PD 124895