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To evaluate whether this effect could be generalized to primary cells, human microvascular endothelial cells were treated with Rottlerin. In this study, we demonstrated that Rottlerin prevents basal and TNF\u03b1\u2010stimulated NF\u03baB nuclear migration and DNA binding also in human microvascular endothelial cell, where NF\u03baB inhibition was accompanied by the downregulation of NF\u03baB target gene products, such as cyclin D\u20101 and endothelin\u20101, which are essential molecules for endothelial cell proliferation and survival. Rottlerin, indeed, inhibited human microvascular endothelial cells proliferation and tube formation on Matrigel. Rottlerin also increases cytoplasmic free calcium and nitric oxide levels and downregulates endothelin converting enzyme\u20101 expression, thus contributing to the drop in endothelin\u20101 and growth arrest. These results suggest that Rottlerin may prove useful in the development of therapeutic agents against angiogenesis.<\/jats:p>","DOI":"10.1111\/j.1747-0285.2011.01121.x","type":"journal-article","created":{"date-parts":[[2011,3,17]],"date-time":"2011-03-17T15:04:39Z","timestamp":1300374279000},"page":"460-470","source":"Crossref","is-referenced-by-count":30,"title":["Rottlerin Exhibits Antiangiogenic Effects <i>In vitro<\/i>"],"prefix":"10.1111","volume":"77","author":[{"given":"Giuseppe","family":"Valacchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Pecorelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Sticozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Torricelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Muscettola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Aldinucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Maioli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,5,4]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2004.12.008"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4165(02)00514-7"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.50.1566"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02151-07"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1199"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.07.003"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105073200"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3510095"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2007.12.020"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2008.00816.x"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/742936"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411758200"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04870"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.8.5785"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.9.1561"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.11.5.9141502"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050136"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(99)00108-6"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.60.6.1332"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0524"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100234200"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404045200"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.11.5681"},{"key":"e_1_2_7_25_2","first-page":"H686","article-title":"Proliferation and migration of endothelial cells is promoted by endothelins via activation of ETB receptors","volume":"269","author":"Morbidelli L.","year":"1995","journal-title":"Am J Physiol"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64807-9"},{"key":"e_1_2_7_27_2","first-page":"42","article-title":"Characterization of endothelin synthetic pathways and receptor subtypes: physiological and pathophysiological implications","volume":"14","author":"Warner T.D.","year":"1993","journal-title":"Eur Heart J"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114477"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(03)01903-4"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.607"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505302200"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.10.066"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-006-0129-3"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-864152"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2007.00143.x"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6057"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00257.2009"}],"container-title":["Chemical Biology &amp; 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