A Daidzein Metabolite, 6,7,4 %26apos;-Trihydroxyisoflavone Inhibits Cellular Proliferation through Cell Cycle Arrest and Apoptosis Induction in MCF10CA1a Human Breast Cancer Cells

作者：Lee Jae Hoo; Lee Hong Jin^*

来源：Journal of the Korean Society for Applied Biological Chemistry, 2013, 56(6): 695-700.

DOI：10.1007/s13765-013-3164-z

• Apoptosis
• Breast Cancer
• Cell Cycle
• Metabolite
• Trihydroxyisoflavone

Despite recent findings of hepatic daidzein metabolites on prevention of skin and colon cancers, little study has been performed on breast cancer. In this study, we found that 6,7,4%26apos;-trihydroxyisoflavone, one of the major hepatic metabolite of the daidzein more significantly inhibited proliferation of MCF10CA1 a human estrogen receptor (ER)-negative breast cancer cells, which was derived from arresting cell cycle at S- and G2/M phase. Cyclins and cyclin-dependent kinases (CDKs) involved in S- and G2/M phases, including cyclins A, B, E, CDK1 and CDK2 were regulated by 6,7,4%26apos;-trihydroxyisoflavone as well as CDK inhibitor, p21 and p27, in a dose-dependent manner. In addition, 6,7,4%26apos;-trihydroxyisoflavone induced apoptosis by enhancing death receptor4 (DR4) expression and suppressing the X-linked inhibitor of apoptosis protein, leading to poly ADP-ribose polymerase cleavage. Taken together, 6,7,4%26apos;-trihydroxyisoflavone inhibits cell proliferation via arresting cell cycle at S- and G2/M phases and inducing apoptosis in MCF10CA1 a human breast cancer cells. These results suggest that the hepatic metabolite of daidzein, 6,7,4%26apos;-trihydroxyisoflavone, may be considered as a more potent agent in inhibiting ER-negative breast carcinogenesis.

• 出版日期2013-12