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Rottlerin Exhibits Antiangiogenic Effects In vitro
Author(s) -
Valacchi Giuseppe,
Pecorelli Alessandra,
Sticozzi Claudia,
Torricelli Claudia,
Muscettola Michela,
Aldinucci Carlo,
Maioli Emanuela
Publication year - 2011
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01121.x
Subject(s) - rottlerin , matrigel , downregulation and upregulation , microbiology and biotechnology , biology , angiogenesis , cancer research , biochemistry , signal transduction , protein kinase c , gene
Rottlerin, a natural product purified from Mallotus philippinensis , has a number of target molecules and biological effects. We recently found that Rottlerin caused growth arrest in MCF‐7 breast cancer cells and human immortalized keratinocytes, through inhibition of NFκB and downregulation of cyclin D‐1. 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 TNFα‐stimulated NFκB nuclear migration and DNA binding also in human microvascular endothelial cell, where NFκB inhibition was accompanied by the downregulation of NFκB target gene products, such as cyclin D‐1 and endothelin‐1, 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‐1 expression, thus contributing to the drop in endothelin‐1 and growth arrest. These results suggest that Rottlerin may prove useful in the development of therapeutic agents against angiogenesis.