ABSTRACT
Angiogenesis, the process of neovascularization, plays an important role in physiological and pathological conditions. ST104P is a soluble polysulfated-cyclo-tetrachromotropylene compound with anti-viral and anti-thrombotic activities. However, the functions of ST104P in angiogenesis have never been explored. In this study, we investigated the effects of ST104P in angiogenesis in vitro and in vivo. Application of ST104P potently suppressed the microvessels sprouting in aortic rings ex vivo. Furthermore, ST104P treatment significantly disrupted the vessels' development in transgenic zebrafish in vivo. Above all, repeated administration of ST104P resulted in delayed tumor growth and prolonged the life span of mice bearing Lewis lung carcinoma. Mechanistic studies revealed that ST104P potently inhibited the migration, tube formation and wound closure of human umbilical endothelial cells (HUVECs). Moreover, ST104P treatment inhibited the secretion and expression of matrix metalloproteinase-2 (MMP-2) in a dose-dependent manner. Together, these results suggest that ST104P is a potent angiogenesis inhibitor and may hold potential for treatment of diseases due to excessive angiogenesis including cancer.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Endothelium, Vascular/drug effects , Macrocyclic Compounds/pharmacology , Matrix Metalloproteinase 2/biosynthesis , Naphthalenesulfonates/pharmacology , Neovascularization, Physiologic/drug effects , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/toxicity , Animals , Animals, Genetically Modified , Aorta , Carcinoma, Lewis Lung/blood supply , Carcinoma, Lewis Lung/drug therapy , Cell Movement/drug effects , Down-Regulation/drug effects , Drug Evaluation, Preclinical , Embryo, Nonmammalian/blood supply , Embryo, Nonmammalian/drug effects , Endothelium, Vascular/enzymology , Endothelium, Vascular/metabolism , Enzyme Induction/drug effects , Human Umbilical Vein Endothelial Cells , Humans , Macrocyclic Compounds/chemistry , Macrocyclic Compounds/therapeutic use , Macrocyclic Compounds/toxicity , Matrix Metalloproteinase 2/metabolism , Mice , Mice, Inbred C57BL , Morphogenesis/drug effects , Naphthalenesulfonates/chemistry , Naphthalenesulfonates/therapeutic use , Naphthalenesulfonates/toxicity , Neovascularization, Pathologic/drug therapy , Zebrafish/embryologyABSTRACT
Breast cancer is the most common cancer in women in the world and the second-most common cancer in women in Taiwan. However, breast cancer with plentiful leukemia blast-like cells circulating in the peripheral blood is very rare. A 48-year-old woman with breast cancer and leukemia-like manifestations was admitted in August, 2006. Special staining and immunophenotyping studies to determine the origin of her peripheral blast cells confirmed that they were from her breast carcinoma. Carcinocythemia (carcinoma cell leukemia) was diagnosed and then systemic chemotherapy and hormone therapy were given. Nevertheless, she expired 9 months after carcinocythemia presentation. The differential diagnosis of this condition, which is complicated by chemotherapy or radiotherapy for solid tumors, is very important. Patients with carcinocythemia have poor prognosis and survival.
