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http://dx.doi.org/10.5352/JLS.2007.17.1.110

Involvement of Early Growth Response Gene 1 (EGR-1) in Growth Suppression of the Human Colonic Tumor Cells By Apigenin and Its Derivative Isovitexin  

Moon, Yu-Seok (Department of Microbiology and Immunology, Medical Research Institute, Pusan National University School of Medicine)
Cui, Lei-Guang (Department of Microbiology and Immunology, Medical Research Institute, Pusan National University School of Medicine)
Yang, Hyun (Department of Microbiology and Immunology, Medical Research Institute, Pusan National University School of Medicine)
Publication Information
Journal of Life Science / v.17, no.1, 2007 , pp. 110-115 More about this Journal
Abstract
It has been previously described that transcription factor early growth response gene product 1 (EGR-1) functions as a tumor suppressor gene. This study was conducted to demonstrate that EGR-1 induction by phytochemical apigenin and its derivative isovitexin can mediate the growth suppression of the intestinal epithelial tumor cells. Apigenin and isovitexin induced EGR-1 gene expression both in the dose and time-dependent manners. Moreover the induction was relatively late around 9-12 hr after treatment of HCT-116 cells, while several anti-inflammatory agent such as NSAIDS and catechins elicit the ECR-1 gene expression at much earlier time about 1-3 hr after treatment. In terms of signal transduction, ERK1/2 was critical for apigenin-induced EGR-1 gene expression and its promoter activation. When EGR-1 gene expression was blocked with EGR-1 small interference RNA, the cytotoxicity of apigenin in the human epithelial cells was attenuated, suggesting the involvement of EGR-1 in the anti-tumoric activity of apigenin. To link the EGR-1 induction to EGR-1-regulated gene products in colon cancer, NSAID-Activated Gene 1 (NAG-1) was demonstrated to be elevated by apigenin and isovitexin at 24-48 hr after treatment. Taken together, apigenin-activated ERK1/2 mediated EGR-1 gene induction, which was associated with suppression of the cellular viability by apigenin compound.
Keywords
EGR-1; apigenin; isovitexin; NAG-1; colon cancer; apoptosis;
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