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A natural metabolite of oestradiol (E2), 2-methoxyoestradiol (2-MeOE2), exerts both antitumour and antiangiogenic effects. 2-MeOE2 is currently in clinical trials for the treatment of a variety of cancers. We have previously shown that a number of sulphamoylated analogues of 2-MeOE2 possess enhanced potency and bioavailability with respect to 2-MeOE2. In our study, the effects of C-2-substituted E2 derivatives, with sulphamoylation at the C-3 and/or C-17 position, on ERalpha -ve MDA-MB-231 breast cancer cells were evaluated. Sulphamoylated derivatives were potent inhibitors of cell proliferation, and these effects were irreversible when compared to growth inhibitory effects induced by 2-MeOE2. Cell cycle analysis suggested that these derivatives caused cells to arrest at the G2-M phase of the cell cycle. Sulphamoylated analogues suppressed the clonogenic potential of MDA-MB-231 cells and also their growth on Matrigel culture substratum. Immunofluorescence studies showed fragmented nuclear bodies and an abnormal microtubule cytoskeleton in cells exposed to one of the potent compounds, 2-MeOE2-bis-sulphamate. In addition, these analogues induced phosphorylation of BCL-2, a protein considered to be the guardian of microtubule integrity. In each of the assays, the sulphamoylated derivatives were at least 10-fold more potent than the parent compound 2-MeOE2. In view of the enhanced potencies associated with sulphamoylated E2 derivatives in ERalpha -ve cells, these analogues should hold considerable therapeutic potential for the treatment of hormone-independent breast cancers.

Original publication




Journal article


Int J Cancer

Publication Date





150 - 159


Breast Neoplasms, Cell Division, Cell Proliferation, Collagen, Drug Combinations, Estradiol, Estrogen Receptor alpha, Female, G2 Phase, Humans, Laminin, Phosphorylation, Proteoglycans, Proto-Oncogene Proteins c-bcl-2, Sulfonic Acids, Tumor Cells, Cultured, Tumor Stem Cell Assay