Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Sulfamoylation of 2-methoxyestrone (2-MeOE1) was shown previously to enhance its potency as an anti-proliferative agent against breast cancer cells. We have examined the ability of a series of 2-methoxyestradiol (2-MeOE2) and 2-ethylestradiol (2-EtE2) sulfamates to inhibit angiogenesis in vitro. 2-MeOE2 bis-sulfamate and 2-EtE2 sulfamate were potent inhibitors of human umbilical vein endothelial cell (HUVEC) proliferation with IC(50) values of 0.05 microM and 0.01 microM, respectively. A novel co-culture system, in which endothelial cells were cultured in a matrix of human dermal fibroblasts, was also used to assess the anti-angiogenic potential of these drugs. In this system endothelial cells proliferate and migrate through the culture matrix to form tubule structures. Whereas 2-MeOE2 (1.0 microM) caused a small reduction in tubule formation, both 2-MeOE2 bis-sulfamate (0.1 microM) and 2-EtE2 sulfamate (0.1 microM) almost completely abolished tubule formation. 2-MeOE2 bis-sulfamate and 2-EtE2 sulfamate both induced BCL-2 phosphorylation, p53 protein expression and apoptosis in HUVECs. Microarray analysis of a limited number of genes known to be involved in the angiogenic process did not show any gross changes in cells treated with the 2-substituted estrogens. The sulfamoylated derivatives of 2-MeOE2 and 2-EtE2 are potent inhibitors of in vitro angiogenesis and both compounds should have therapeutic potential.

Original publication

DOI

10.1002/ijc.20045

Type

Journal article

Journal

Int J Cancer

Publication Date

20/04/2004

Volume

109

Pages

533 - 540

Keywords

Angiogenesis Inhibitors, Apoptosis, Cell Movement, Cells, Cultured, Coculture Techniques, Endothelial Cells, Estradiol, Fibroblasts, Gene Expression Profiling, Humans, Neovascularization, Pathologic, Oligonucleotide Array Sequence Analysis, Phosphorylation, Proto-Oncogene Proteins c-bcl-2, Skin, Sulfonic Acids, Tumor Suppressor Protein p53