To investigate the effects of equol on cell cycle distribution and apoptosis in human breast cancer cells, we first determined the antiproliferative effects of various concentrations of equol (1 nM to 100 µM) on MCF-7 and MDA-MB-453 cells at 24, 48 or 72 h of exposure. Equol significantly inhibited proliferation in MDA-MB-453 cells in a dose- and time-dependent manner. In contrast, equol at low concentrations (<1 µM) stimulated proliferation in MCF-7 cells, with increased expression of proliferating cell nuclear antigen (PCNA), and only inhibited proliferation at a high concentration (100 µM). Similarly, equol treatment of MDA-MB-453 cells resulted in significant cell cycle arrest at the G1/S transition and in the G2/M phase, whereas it caused the slight cell cycle arrest of MCF-7 cells in the G2/M phase after 72 h of treatment. Also, when cells were treated with 50 and 100 µM equol for 72 h, the equol affected cell cycle regulatory proteins more significantly in MDA-MB-453 than in MCF-7 cells. During equol-induced apoptosis, equol increased the number of cells in the sub-G0 phase and enhanced the level of p53. The expression of Bax and cytochrome c, downstream targets of p53, was markedly increased by treatment with higher concentrations of equol. Equol-induced cell cycle arrest and apoptosis apparently involves a p53-dependent pathway in different types of breast cancer cells.

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