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  • Title: [Inhibition of angiogenesis by antitumor antibiotic C1027 and its effect on tumor metastasis].
    Author: Zhen H, Xue Y, Zhen Y.
    Journal: Zhonghua Yi Xue Za Zhi; 1997 Sep; 77(9):657-60. PubMed ID: 9772532.
    Abstract:
    OBJECTIVE: To investigate the effect of C1027, an enediyne antitumor antibiotic, on angiogenesis and its anti-metastatic activity. METHODS: Chick embryo chorioallantoic membrane assay was used for anti-angiogenesis activity and bFGF receptor binding assay was used for the elucidation of the possible mechanism. Spontaneous pulmonary metastasis of Lewis carcinoma in mice was employed to evaluate the anti-metastatic effect. RESULTS: C1027 was highly potent in suppressing angiogenesis with a minimum effective dose of 0.01 microgram/egg. Enediyne chromophore moiety of the C1027 molecule was essential to anti-angiogenesis activity. Receptor binding assay showed that C1027 blocked bFGF binding to its receptor with an IC50 value of 2.3 x 10(-6) micrograms/ml. C1027 markedly inhibited pulmonary metastasis of Lewis carcinoma in mice. Compared at equitoxic dosage level (1/4 LD50), C1027 (0.01 mg/kg, i.v., x 2) was more effective than mitomycin (1.25 mg/kg, i.v., x 2) and the percent inhibition of metastatic foci in the lung was 98% and 78%, respectively. CONCLUSIONS: C1027 is a new potent anti-angiogenesis agent with markedly anti-metastatic activity. The mechanism of C1027 suppressing angiogenesis may be related to its blocking effect on bFGF binding to its receptor.
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