title: Baicalein suppresses 17-β-estradiol-induced migration, adhesion and invasion of breast cancer cells via the G protein-coupled receptor 30 signaling pathway.
abstract: Flavonoids are structurally similar to steroid hormones, particularly estrogens, and therefore have been studied for their potential effects on hormone-dependent cancers. Baicalein is the primary flavonoid derived from the root of Scutellaria baicalensis Georgi. In the present study, we investigated the effects of baicalein on 17β-estradiol (E2)-induced migration, adhesion and invasion of MCF-7 and SK-BR-3 breast cancer cells. The results demonstrated that baicalein suppressed E2-stimulated wound-healing migration and cell‑Matrigel adhesion, and ameliorated E2-promoted invasion across a Matrigel-coated Transwell membrane. Furthermore, baicalein interfered with E2-induced novel G protein-coupled estrogen receptor (GPR30)-related signaling, including a decrease in tyrosine phosphorylation of epidermal growth factor receptor (EGFR) as well as phosphorylation of extracellular signal-regulated kinase (ERK) and serine/threonine kinase Akt, without affecting GPR30 expression. The results also showed that baicalein suppressed the expression of GPR30 target genes, cysteine-rich 61 (CYR61) and connective tissue growth factor (CTGF) induced by E2. Furthermore, baicalein prevented GPR30-related signaling activation and upregulation of CYR61 and CTGF mRNA levels induced by G1, a specific GPR 30 agonist. The results suggest that baicalein inhibits E2-induced migration, adhesion and invasion through interfering with GPR30 signaling pathway activation, which indicates that it may act as a therapeutic candidate for the treatment of GPR30-positive breast cancer metastasis.
authors: Department of Physiology/Cancer Research Group, Guiyang Medical University School of Basic Medicine, Guiyang, Guizhou 550004, P.R. China.
authors: Dandan
authors: D
authors: Shang
authors: Department of Physiology/Cancer Research Group, Guiyang Medical University School of Basic Medicine, Guiyang, Guizhou 550004, P.R. China.
authors: Zheng
authors: Z
authors: Li
authors: Department of Physiology/Cancer Research Group, Guiyang Medical University School of Basic Medicine, Guiyang, Guizhou 550004, P.R. China.
authors: Zhuxia
authors: Z
authors: Zhu
authors: Department of Physiology/Cancer Research Group, Guiyang Medical University School of Basic Medicine, Guiyang, Guizhou 550004, P.R. China.
authors: Huamei
authors: H
authors: Chen
authors: Department of Pharmacology of Chinese Material Medica, Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors: Lujun
authors: L
authors: Zhao
authors: Department of Physiology/Cancer Research Group, Guiyang Medical University School of Basic Medicine, Guiyang, Guizhou 550004, P.R. China.
authors: Xudong
authors: X
authors: Wang
authors: Department of Pharmacology of Chinese Material Medica, Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors: Yan
authors: Y
authors: Chen
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D002448:Cell Adhesion / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D055513:Connective Tissue Growth Factor / Q000235:genetics; D055515:Cysteine-Rich Protein 61 / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C501848:CCN1 protein, human; C526317:CCN2 protein, human; D055515:Cysteine-Rich Protein 61; D044950:Flavanones; C109584:GPER1 protein, human; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D055513:Connective Tissue Growth Factor; C006680:baicalein; D004958:Estradiol; C512478:EGFR protein, human; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases