The licorice flavonoid isoliquiritigenin suppresses phorbol ester-induced cyclooxygenase-2 expression in the non-tumorigenic MCF-10A breast cell line.
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.
Lau
Grace Tak
GT
Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong.
Ye
Lan
L
Leung
Lai K
LK
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*
D047188:Chalcones; D017931:DNA Primers; C040920:isoliquiritigenin; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate