title: The licorice flavonoid isoliquiritigenin suppresses phorbol ester-induced cyclooxygenase-2 expression in the non-tumorigenic MCF-10A breast cell line.
abstract: Cyclooxygenase (COX) is the rate-limiting enzyme for the conversion of prostaglandins from arachidonic acid. Upregulation of COX-2 has been well documented during tumorigenesis and metastasis of breast cancer. Isoliquiritigenin (ILN), a flavonoid isolated from licorice (the rhizomes of GLYCYRRHIZA GLABRA, a member of the bean plant family), is known to be a potential suppressor of COX-2 expression. This study focuses on phorbol ester-induced COX-2 expression in the non-tumorigenic MCF-10A cells. Real-time PCR and Western blotting indicated that ILN at 5 microM or above significantly inhibited phorbol 12-myristate 13-acetate (PMA)-induced COX-2 expression in the breast cells. The activated PKC alpha appeared to be not affected, whereas its downstream mitogen-activated protein kinase (MAPK) ERK-1/2 was deactivated. ERK can activate the transcriptional factor binding of AP-1 or CRE, which can be located at the COX-2 promoter region (- 72/- 53). Electrophoretic mobility shift assays illustrated that ILN suppressed DNA binding at this region. The shifted bands could be competed off with consensus sequences of AP-1 and CRE, and the supershift assay demonstrated that CREB-1 instead of c-Jun was responsible for the binding. This study showed that ILN downregulated PMA-induced COX-2 expression by modulating ERK-1/2 signaling, a finding that may be relevant to the disease prevention properties of licorice.
authors.affiliation: Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong.
authors.forename: Grace Tak
authors.initials: GT
authors.lastname: Lau
authors.forename: Lan
authors.initials: L
authors.lastname: Ye
authors.forename: Lai K
authors.initials: LK
authors.lastname: Leung
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D017931:DNA Primers; D015232:Dinoprostone / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006035:Glycyrrhiza / Q000737:chemistry*; D006801:Humans; D016133:Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D047188:Chalcones; D017931:DNA Primers; C040920:isoliquiritigenin; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate