Abstract
The anti-tumor activity of diosgenin, a new steroidal constituent present in fenugreek, on two human breast cancer cell lines, MCF-7 and Hs578T, was studied. Diosgenin treatment resulted in cell growth inhibition, cell cycle arrest, and apoptosis in concentration- and time-dependent manners in both cell lines. Western blot analyses of whole cell lysates for cell cycle proteins showed that diosgenin altered phosphorylated cyclin checkpoint1 (p-Chk1Ser345) and cyclin B expression, which resulted in G2/M phase blockade. Mechanistically, Cdc25C-Cdc2 signaling was involved in inactivating Chk1Ser345 by p53-dependence in MCF-7 cells and p21-dependence in Hs578T cells that are p53-deficient. Moreover, diosgenin induced a significant loss of the mitochondrial membrane potential in breast cancer cells, and prominently affected cell death through down-regulation of the anti-apoptotic protein, Bcl-2. This released cytochrome c and activated the caspase signaling cascade. Taken together, these findings reveal that the anti-proliferative activity of diosgenin involves the induction of G2/M phase arrest via modulating the Cdc25C-Cdc2-cyclin B pathway and mitochondria-mediated apoptosis in human breast cancer cell lines. This suggests the potential usefulness of diosgenin in treating breast cancer.
Highlights
Breast cancer is the most common malignancy among women and the second leading cause of cancer-related death in the United States
These findings indicated that both MCF-7 and Hs578T cells were sensitive to diosgenin treatments; we selected these two breast cancer cell lines to perform further analyses and evaluate the anti-tumor property of diosgenin
The results of the present study demonstrated that diosgenin exerted an anti-tumor activity on two human breast cancer cell lines, MCF-7 and Hs578T
Summary
Breast cancer is the most common malignancy among women and the second leading cause of cancer-related death in the United States (http://seer.cancer.gov). To our knowledge, the ability of diosgenin to inhibit breast cancer cells has not been fully explored, and there is no evidence that the anticancer capability of diosgenin shown in vitro will affect the cell cycle checkpoint kinases (Chks) that control tumorigenesis. To this end, we determined the anti-proliferative activity of diosgenin by using two human breast cancer cell lines, MCF-7 and Hs578T, as in vitro models. The results provided the first information on the ability of diosgenin to inhibit various breast cancers
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