Effects of thalidomide, cytochrome P-450 and TNF-alpha on angiogenesis in a three-dimensional collagen gel-culture.
The anti-angiogenic effects of thalidomide were examined in mouse aortae grown in a three-dimensional collagen gel-culture. In our in vitro model, (+/-)-thalidomide and (-)-thalidomide exhibited no anti-angiogenic effects. On the other hand, when the culture was treated with thalidomide plus cytochrome P-450, both types of thalidomides significantly inhibited angiogenesis. Co-administration of 100 microg/ml thalidomide plus 200 microg/ml cytochrome P-450 inhibited angiogenesis more strongly than thalidomide plus cytochrome P-450 at other concentrations (10 microg/ml + 200 microg/ml and 100 microg/ml + 20 microg/ml). To study the relation between the anti-angiogenic effect and TNF-alpha, we also evaluated the concentration of TNF-alpha in the culture medium. We found that the concentration of TNF-alpha was correlated to the strength of the anti-angiogenic effect. The inhibition of angiogenesis by thalidomide and cytochrome P-450 takes place through a suppression of TNF-alpha and involves the metabolism of the thalidomide.
Fujita
Keiko
K
Department of Anatomy, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan. kfujita@saitama-med.ac.jp
Asami
Yoshiko
Y
Murata
Eiko
E
Akita
Masumi
M
Kaneko
Katsuji
K
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology*; D003584:Cytological Techniques; D005782:Gels; D051379:Mice; D008813:Mice, Inbred ICR; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D013792:Thalidomide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D005782:Gels; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D003094:Collagen; D003577:Cytochrome P-450 Enzyme System