Abstract 5491: Antiangiogenic mechanism studies of a new heparin derived angiogenesis inhibitor, LHT7

In the past decades, chemotherapy was the major treatment for cancer. Cancer chemotherapy, however, relies on its cytotoxicity towards rapidly dividing cells affecting proliferating normal cells also resulting in harmful or undesirable side effects. Therefore developing anti-cancer drugs having more selectivity to tumor cells is the most important goal of anti-cancer drug development. One avenue to develop ideal anti-cancer drug is to target the process of tumor angiogenesis critical for tumor growth but not a frequent biological process in adults, thus providing more selectivity towards cancer. Angiogenesis refers to a development of new blood vessels and is a crucial physiological process on embryonic development, tissue repair, fertility and also on tumor growth. It is a critical process for tumor growth and is regulated by tumor cell-derived factors that have mitogenic and chemotactic effects on vascular endothelial cells. Many basic and clinical studies manifested that suppression of angiogenesis inhibited tumor progression and metastasis. The strategy to inhibit tumor angiogenesis can be achieved by blocking the activity of tumor cell-derived factors that are responsible for tumor angiogenesis. Vascular endothelial growth factor (VEGF) is one such key regulator having most weight on angiogenesis among various factors that are involved in. So by blocking VEGF signaling pathway, angiogenesis can be suppressed resulting in cancer inhibition. We have chosen heparin to be the mother molecule of new candidate for anti-angiogenesis agent. Heparin is known to have antiangiogenesis effect, thus having potential for tumor suppression, through interacting with various proteins such as enzymes, cytokines and growth factors involved in angiogenesis. In spite of heparins biological effect on suppressing tumor growth, heparin-based therapeutic approach towards cancer has limitation because of its insufficient anticancer effect and its strong anticoagulant effect, which can cause severe hemorrhage when applied in high dose. To overcome these clinical limitations, we have developed a chemically modified heparin, a low-molecular-weight heparin and taurocholic acid conjugation (LHT7), having enhanced antiangiogenic effect and almost none of anticoagulant activity. In the previous studies, we have evaluated LHT7s anticancer effect and antiangiogenesis effect. And within current research we have studied about its antiangiogenic mechanisms that induced its biological effe