Deguelin Inhibits Growth of Breast Cancer Cells by Modulating the Expression of Key Members of the Wnt Signaling Pathway

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Abstract
An emphasis in early detection and more effective treatments has decreased the mortality rate of breast cancer. Despite this decrease, breast cancer continues to be the leading cause of death among women between 40 and 55 years of age and is the second overall cause of death among women. Hence, the aim of the present study was to assess the therapeutic efficacy of deguelin, a rotenoid isolated from several plant species, which has been reported to have chemopreventive and/or chemotherapeutic effects in skin, mammary, colon, and lung cancers. The effect of deguelin on cell proliferation was evaluated using four human breast carcinoma cell lines (MCF-7, BT474, T47D, and MDA-MB-231) by cell count and MTT. Moreover, apoptosis was evaluated by acridine/ethidium staining and DNA laddering. Gene expression changes following deguelin treatment in MDA-MB-231 cells was assessed through microarray analysis. Deguelin at 1 μmol/L was found to inhibit the growth of the breast cancer cell lines tested with a range of 37% to 87%. The highest inhibition was noted for the MDA-MB-231 cell line (MDA-MB-231>BT474>MCF7>T47D>MCF12F). An arrest at the S phase of the cell cycle and apoptosis were shown in the MDA-MB-231 cells treated with deguelin. The microarray profile indicated differential expression of two independent pathways, including clusters of apoptosis and Wnt/β-catenin signaling genes in cells as a result of deguelin treatment. These studies support the antiproliferative effects of deguelin in human breast cancer cells and, perhaps more importantly, illustrate novel actions by deguelin in the Wnt signaling pathway.