Inhibition of endothelial cell functions by novel potential cancer chemopreventive agents |
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Authors: | Bertl Elisabeth Becker Hans Eicher Theophil Herhaus Christian Kapadia Govind Bartsch Helmut Gerhäuser Clarissa |
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Affiliation: | Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. |
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Abstract: | Endothelial cells (EC) play a major role in tumor-induced neovascularization and bridge the gap between a microtumor and growth factors such as nutrients and oxygen supply required for expansion. Immortalized human microvascular endothelial cells (HMEC-1) were utilized to assess anti-endothelial effects of 10 novel potential cancer chemopreventive compounds from various sources that we have investigated previously in a human in vitro anti-angiogenic assay. These include the monoacylphloroglucinol isoaspidinol B, 1,2,5,7-tetrahydroxy-anthraquinone, peracetylated carnosic acid (PCA), isoxanthohumol, 2,2',4'-trimethoxychalcone, 3'-bromo-2,4-dimethoxychalcone as well as four synthetic derivatives of lunularic acid, a bibenzyl found in mosses [Int. J. Cancer Prev. 1 (2004) 47]. EC proliferation was inhibited with half-maximal inhibitory concentrations from 0.3 to 49.6muM, whereas EC migration was affected by most compounds at sub-micromolar concentrations. PCA and the bibenzyl derivative EC 1004 potently prevented differentiation of HMEC-1 into tubule-like structures. Overall, our data indicate that inhibition of endothelial cell function contributes to various extents to the chemopreventive or anti-angiogenic potential of these lead compounds. |
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Keywords: | Anti-angiogenic Anti-endothelial Bibenzyls Cancer chemoprevention Chalcones Human microvascular endothelial cells Migration Polyphenols Proliferation Tube formation HCT-116 SK-BR3 NIH/3T3 |
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