Abstract
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′-trihydroxyisoflavone, one of the major hepatic metabolite of the daidzein more significantly inhibited proliferation of MCF10CA1a 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′-trihydroxyisoflavone as well as CDK inhibitor, p21 and p27, in a dose-dependent manner. In addition, 6,7,4′-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′-trihydroxyisoflavone inhibits cell proliferation via arresting cell cycle at S- and G2/M phases and inducing apoptosis in MCF10CA1a human breast cancer cells. These results suggest that the hepatic metabolite of daidzein, 6,7,4′-trihydroxyisoflavone, may be considered as a more potent agent in inhibiting ER-negative breast carcinogenesis.
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Lee, J.H., Lee, H.J. A daidzein metabolite, 6,7,4′-trihydroxyisoflavone inhibits cellular proliferation through cell cycle arrest and apoptosis induction in MCF10CA1a human breast cancer cells. J Korean Soc Appl Biol Chem 56, 695–700 (2013). https://doi.org/10.1007/s13765-013-3164-z
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DOI: https://doi.org/10.1007/s13765-013-3164-z