Antitumor Antibiotic C1027 Inhibition Of Angiogenesis And Tumor Metastasis And Its Mechanism Of Action Study

The growth of neoplasms highly rely on angiogenesis. Primary tumor of 1-2 mm in diameter can receive all nutrients by diffusions; however, further growth depends on the development of an adequate blood supply through angiogenesis. Moreover, new blood vessels penetrating the tumor are frequent sites for tumor cell entering into the circulation. Angiogenesis is also required for the expansion of metastatic colonies. Basic fibroblast growth factor, bFGF, is characterized by its high affinity to heparin and obvious mitogen to endothelial cells and several other types of mesoderm and neuroectoderm-derived cells. bFGF becomes the major angiogenesis inducer for its special trifunctional stimulation of capillary endothelial cells. This triad of functions consists of cell motility, proliferation and proteolysis. The inhibition of angiogenesis may prevent the growth of tumor cells at both the primary and secondary sites and thus can prevent the emergence of metastasis, such as pulmonary metastases of murine Lewis carcinoma. Therefore, anti-angiogenesis provides a novel and more general approach for treatment of cancers and the metastases.We used chick embryo chorioallantoic membrane (CAM) assay for anti-angiogenesis activity. After examining a series of compounds, we found that C1027, an enediyne antitumor antibiotic, was highly potent in suppressing angiogenesis. When the doses of C1027 were at 0.01 μg/egg, 0.05 μg/egg and 0.1 μg/egg, the inhibition of CAM angiogenesis reached 70%, 90% and 100%, respectively. C1027 at dose of 1 /zg/egg was lethal. Used as positive control, minocycline and hydrocortisone at doses of 30 μg/egg and 60 μg/egg showed 70% and 50% inhibition, respectively. As known, the molecule of C1027 is composed of an enediyne chromophore and an apoprotein...