Suppression of Transcription Factor Egr-1 by Curcumin

• Published in: Thrombosis research 2000-02, Vol.97 (4), p.179-189
• Main Authors: Pendurthi, Usha R, Rao, L.Vijaya Mohan
• Format: Article
• Language: English
• Subjects: Binding Sites; Biological and medical sciences; Blood; Cells, Cultured; Curcumin; Curcumin - pharmacology; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drug Interactions; Early Growth Response Protein 1; Egr-1; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Fibroblasts - drug effects; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Humans; Immediate-Early Proteins; Receptors, Cell Surface - antagonists & inhibitors; Receptors, Cell Surface - metabolism; Receptors, Urokinase Plasminogen Activator; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Tetradecanoylphorbol Acetate - antagonists & inhibitors; Tetradecanoylphorbol Acetate - pharmacology; Thromboplastin - antagonists & inhibitors; Thromboplastin - metabolism; Tissue factor; Transcription Factors - antagonists & inhibitors; Transcription Factors - genetics; Transcription Factors - metabolism; Vertebrates: blood, hematopoietic organs, reticuloendothelial system
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/S0049-3848(99)00148-6

The transcription factor early growth response-1 gene product (Egr-1) is a member of the family of immediate early response genes and regulates a number of pathophysiologically relevant genes in vasculature that are involved in growth, differentiation, immune response, wound healing, and blood clotting. In the present study, we investigated the effect of curcumin, a natural plant phenolic compound known to exhibit anticarcinogenic, antioxidant, and antiinflammatory properties, on Egr-1 expression in endothelial cells and fibroblasts. Gel mobility shift assays showed that pretreatment of endothelial cells and fibroblasts with curcumin suppressed phorbol 12-myristate 13-acetate and serum-induced Egr-1 binding activity to the consensus Egr-1 binding site and also to the Egr-1 binding site present in the promoter of tissue factor gene. Western blot analysis revealed that curcumin inhibited phorbol 12-myristate 13-acetate-induced de novo synthesis of Egr-1 protein in endothelial cells. Suppression of Egr-1 protein expression in curcumin-treated cells stemmed from the suppression of Egr-1 mRNA. Northern blot analysis showed that curcumin inhibited serum and phorbol 12-myristate 13-acetate induced expression of tissue factor and urokinase-type plasminogen activator receptor mRNA in fibroblasts. Cumulatively, the data show that curcumin suppresses the induction of transcription factor Egr-1 and thereby modulates the expression of Egr-1-regulated genes in endothelial cells and fibroblasts.