2-MeOE2 bisMATE and 2-EtE2 bisMATE induce cell cycle arrest and apoptosis in breast cancer xenografts as shown by a novel ex vivo technique.

Autor: Foster, Paul A., Ho, Yaik T., Newman, Simon P., Kasprzyk, Philip G., Leese, Mathew P., Potter, Barry V. L., Reed, Michael J., Purohit, Atul
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Zdroj: Breast Cancer Research & Treatment; Sep2008, Vol. 111 Issue 2, p251-260, 10p, 1 Color Photograph, 1 Diagram, 1 Chart, 5 Graphs
Abstrakt: Breast cancer is the leading cause of cancer deaths among women worldwide. The theory of targeting both cancer cells directly and their blood supply has significant therapeutic potential. However, to date, there are few clinically successful single agents that meet these criteria. 2-Methoxyestradiol-3,17- O, O- bis-sulfamate (2-MeOE2 bisMATE) and 2-ethylestradiol-3,17- O, O- bis-sulfamate (2-EtE2 bisMATE) are potent inhibitors of proliferation in a range of cancer cells. The work presented here demonstrates the potent in vitro and in vivo effects of these compounds. They cause apoptosis via the intrinsic mitochondrial pathway in both MDA-MB-231 breast cancer cells and endothelial cells. Furthermore, they are potent anti-angiogenic inhibitors in vivo, as shown by their ability to reduce endothelial staining in MDA-MB-231 xenograft tumors. We have developed a novel, flow cytometry based, ex vivo method which shows in cells recovered from MDA-MB-231 tumors treated with 2-MeOE2 bisMATE and 2-EtE2 bisMATE an increase in intra-tumoral G2-M arrest and apoptosis. The degree of apoptosis inversely correlates to tumor volume. Further in vivo studies reveal that both 2-MeOE2 bisMATE and 2-EtE2 bisMATE are orally bioavailable and extremely efficacious when compared to clinically tested drugs. As these compounds are anti-proliferative against breast cancer and endothelial cells they have the potential to be potent, dual acting clinical drugs of the future. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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