Baicalein has protective effects on the 17β-estradiol-induced transformation of breast epithelial cells.

Epidemiologic and systematic studies have indicated that flavonoid consumption is associated with a lower incidence of breast cancer. Baicalein is the primary flavonoid derived from the roots of Scutellaria baicalensis Georgi. In the current study, the long-term exposure of breast epithelial cells to 17β-estradiol (E2) was used to investigate the chemopreventive potential of baicalein on neoplastic transformation. The results demonstrated that baicalein significantly inhibited E2-induced cell growth, motility, and invasiveness, and suppressed E2-induced misshapen acini formation in 3D cultures. Furthermore, it inhibited the ability of E2-induced cells to form clones in agarose and tumors in NOD/SCID immunodeficient mice. Docking studies using Sybyl-X 1.2 software showed that baicalein could bind to both estrogen receptor-α (ERa) and G-protein coupled estrogen receptor 30 (GPR30), which are two critical E2-mediated pathways. Baicalein prevented the E2-induced ERa-mediated activation of nuclear transcriptional signaling by interfering with the trafficking of ERa into the nucleus and subsequent binding to estrogen response elements, thereby decreasing the mRNA levels of ERa target genes. It also inhibited E2-induced GPR30-mediated signal transduction, as well as the transcription of GPR30-regulated genes. Therefore, these results suggest that baicalein is a potential drug for reducing the risk of estrogen-dependent breast cancer.