In summary, our data provide support for decursin and DA as potential novel breast cancer chemopreventive agents by targeting ERα signaling through inhibiting its transcription, stability and abundance as well as nuclear translocation in estrogen-dependent MCF-7 cells, and by inducing ERβ in estrogen-independent MDA-MB231 cells, leading to cell-cycle arrest and proapoptotic actions. The gene discussed is ESR2; the disease is breast cancer.