Anti-angiogenic effects of thalidomide: expression of apoptosis-inducible active-caspase-3 in a three-dimensional collagen gel culture of aorta.
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-alpha and inhibition of cell migration from aorta explants, i.e., the factors important for capillarogenesis.
Fujita
Keiko
K
Department of Anatomy, Saitama Medical School, 38 Moroyama, Iruma-gun, 350-0495 Saitama, Japan. kfujita@saitama-med.ac.jp
Asami
Yoshiko
Y
Tanaka
Kayoko
K
Akita
Masumi
M
Merker
Hans-Joachim
HJ
D043924:Angiogenesis Modulating Agents / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D018929:Cell Culture Techniques / Q000379:methods; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D000072467:Cytochrome P450 Family 2; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011817:Rabbits; D013792:Thalidomide / Q000494:pharmacology*
D043924:Angiogenesis Modulating Agents; D013792:Thalidomide; D003094:Collagen; D001189:Aryl Hydrocarbon Hydroxylases; D000072467:Cytochrome P450 Family 2; C465241:cytochrome P-450 CYP2B4 (rabbit); C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases