Affiliation: | (1) Department of Anatomy, Saitama Medical School, 38 Moroyama, Iruma-gun, 350-0495 Saitama, Japan;(2) Division of Morphological Science, Biomedical Research Center, Saitama Medical School, 38 Moroyama, Iruma-gun, 350-0495 Saitama, Japan;(3) Institute of Anatomy, Free University of Berlin, Königin-Luise-strasse 15, 14195 Berlin, Germany |
Abstract: | The anti-angiogenic properties of thalidomide have led to the use of the agent as a remedy for multiple myeloma. Nevertheless, the anti-angiogenic moiety of thalidomide remains unidentified. In this study we examined the anti-angiogenic effects of thalidomide in an in vitro model using a three-dimensional collagen gel culture. Angiogenesis was significantly inhibited when the culture was treated with thalidomide plus cytochrome P-450 (CYP2B4), and the migrating cells and tubules were positive for active-caspase-3 in an accompanying immunohistochemical investigation. Transmission electron microscopic observation also confirmed that active-caspase-3-positive cells demonstrated apoptotic characteristics. This study is the first to morphologically demonstrate the effect of thalidomide in directly inducing the apoptosis of new tubules and migrating cells on a three-dimensional collagen gel culture of aorta. Taken together with earlier findings, our new results indicate that the thalidomide-induced inhibition of angiogenesis involves apoptosis in addition to the suppression of TNF- and inhibition of cell migration from aorta explants, i.e., the factors important for capillarogenesis. |