Inhibition of Angiogenesis by Anthracyclines and Titanocene Dichloride
| Autor: | Paraskevi Andriopoulou, George C. Haralabopoulos, Platon Peristeris, Alexis J. Aletras, E. Missirlis, Michael E. Maragoudakis |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Umbilical Veins Matrix metalloproteinase inhibitor Daunorubicin Angiogenesis Antineoplastic Agents Chick Embryo Matrix Metalloproteinase Inhibitors General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley Neovascularization History and Philosophy of Science Allantois Organometallic Compounds Tumor Cells Cultured medicine Animals Humans Doxorubicin Carcinoma 256 Walker Cytotoxicity Cells Cultured Skin Tube formation Matrigel Antibiotics Antineoplastic Neovascularization Pathologic Chemistry General Neuroscience Chorion Fibroblasts Rats Gelatinases Cancer research Collagen Endothelium Vascular medicine.symptom Chickens medicine.drug |
| Zdroj: | Annals of the New York Academy of Sciences. 732:280-293 |
| ISSN: | 1749-6632 0077-8923 |
| Popis: | The anthracycline antibiotics, daunorubicin, doxorubicin, and epirubicin, which are widely used for treatment of malignancies, have been evaluated for their effect on angiogenesis in relation to the inhibition of collagenase type IV reported previously. In the chick chorioallantoic membrane (CAM) system of angiogenesis, anthracyclines inhibited vascular density at doses of 5-20 micrograms/disc as well as collagenous protein biosynthesis, which is a reliable index of angiogenesis. Similarly, all three anthracyclines inhibited tube formation in the in vitro system of angiogenesis using human umbilical vein endothelial cells (HUVECs) plated on Matrigel. The inhibition was dose-dependent and caused 50% inhibition at concentrations of 2.5-15 micrograms/mL. At concentrations of anthracyclines which prevented tube formation and angiogenesis, there were no cytotoxic effects, as evidenced by methylene blue uptake, and the growth of these endothelial cells was not inhibited. The experimental antitumor agent titanocene dichloride inhibited collagenase type IV from Walker 256 carcinosarcoma with IC50 approximately 0.2 mM. Titanocene also prevented angiogenesis in the CAM and tube formation by HUVECs on Matrigel at concentrations that were without effect on growth or cytotoxicity of endothelial cells or Walker 256 cells in culture. The antiangiogenic effect of the aforementioned antitumor agents at therapeutically attainable concentrations may explain, at least in part, their antitumor properties because angiogenesis is an essential process for tumor growth and metastasis. The antiangiogenic effect is, however, unrelated to metalloproteinase inhibition because higher concentrations are required for that effect than for inhibition of angiogenesis. |
| Databáze: | OpenAIRE |
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