title: Baicalein has protective effects on the 17β-estradiol-induced transformation of breast epithelial cells.
abstract: 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.
authors.affiliation: The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.|Department of Pharmacology of Chinese Material Medica, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.
authors.forename: Duan-Yang
authors.initials: DY
authors.lastname: Hong
authors.affiliation: The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.
authors.forename: Yi-Ni
authors.initials: YN
authors.lastname: Xu
authors.affiliation: The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.|Department of Pharmacology of Chinese Material Medica, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Pan
authors.affiliation: The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.|Department of Pharmacology of Chinese Material Medica, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Fu
authors.affiliation: The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
authors.affiliation: The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Luo
authors.affiliation: The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.|Department of Pharmacology of Chinese Material Medica, Guizhou Medical University, Huaxi university town, Guian new district 550025, Guizhou, People's Republic of China.
authors.forename: Xiang-Chun
authors.initials: XC
authors.lastname: Shen
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000633:toxicity*; D004965:Estrogen Antagonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D011960:Receptors, Estrogen / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D016588:Anticarcinogenic Agents; C506487:ESR1 protein, human; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D005419:Flavonoids; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C413305:baicilein; D004958:Estradiol
keywords: 17β-estradiol; baicalein; breast cancer; chemoprevention; estrogen receptor