Studies Of Anti-angiogenic And Anti-metastatic Activity Of Lidamycin And Emodin And The Mechanisms

One of the most promising and intense areas of cancer research focuses on the discovery of agents that inhibit tumor angiogenesis. The excitement surrounding angiogenesis inhibitors stems largely from the speculation that anti-angiogenesis therapy will be effective against a wide variety of tumors and selective to tumor vasculature without affecting other tissues. Tumor growth and metastasis are depended on angiogenesis, therefore, an anti-angiogenic strategy might be effective as an anticancer therapy.Lidamycin (LDM), a new macromolecular antibiotic with an enediyne chromophore, displays extremely potent cytotoxicity against cancer cells. The previous study in our lab demonstrated its anti-angiogenic and anti-metastatic activities. In this study, its mechanisms of action were investigated. Emodin (3-methyl-1,6,8 trihydroxyanthraquinone), isolated from Polygonum cuspidatum, is an inhibitor of protein tyrosine kinase. It has wide biological activities, however, its anti-angiogenic and anti-metastatic activities have not been reported until now. In this study, we first observed its anti-angiogenic and anti-metastatic activities. Furthermore, the mechanisms of its actions were studied. The main results are as follows.1. Mechanisms of the anti-angiogenic and anti-metastatic activity of LDM.LDM could inhibit angiogenesis dramatically. CAM assay demonstrated that LDM exhibited potent anti-angiogenic activity with a minimum effective dose of 0.01 ug/egg. LDM at 0.1 ug/egg inhibited the angiogenesis of CAM completely.LDM showed potent anti-proliferative activity on endothelial cells. Growth inhibitory effects of LDM on two kinds of endothelial cells, bovine aortic vessel endothelial cells (BAVECs) and a transformed endothelial cell line established from human umbilical cord vein (ECV304 cells), were determined by MTT assay, [~3H] thymidine incorporation assay and clonogenic assay. The results showed that LDM inhibited the proliferation of BAVECs with or without the stimulation of basic-fibroblast growth factor (bFGF) in a dose- and time-dependent...