Objective:To investigate whether dietary daidzein interact with endogenous 17β-Estradiol (E2) to give rise to additive or inhibitory effects on proliferation and apoptosis in breast cancer cells.Methods:Cell cycle distribution and apoptosis induction were analyzed by using flow cytometry when breast cancer cell lines MCF-7 were cotreated with daidzein (1, 5 μmol/L) and E2 (0.1-10 nmol/L) for 5 days. Whether daidzein could alter E2-modulated mRNA expression of estrogen receptor alpha (ERa), estrogen receptor beta (ERβ) and ERβ-estrogen response element (ERE) dependent transcription was investigated by RT-PCR and luciferase induction assays. The effects of daidzein on E2-modulated expression of proapoptotic p53, bax and antiapoptotic bcl-2 at both mRNA and protein levels were also investigated by RT-PCR and West blot. Results:Daidzein enhanced the antiapoptotic effect in an E2 dose-dependent manner, but had no effect on E2-induced proliferation. Daidzein antagonized E2-induced ERβ mRNA expression and ERβ-ERE dependent transcription. In addition, daidzein only antagonized E2-upregulated expression of p53 and bax, but had no effect on E2-upregulated expression of bcl-2. Conclusion:Daidzein enhances the antiapoptotic effect of E2 on breast cancer cells by inhibiting E2-mediated p53-bax proapoptotic pathway. These results suggest that dietary daidzein may enhance deleterious effect of endogenous E2 in hormone-dependent breast cancer.