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KMID : 0829220090330040213
Korean Journal of Oral and Maxillofacial Pathology
2009 Volume.33 No. 4 p.213 ~ p.218
Molecular Changes and Effects of Epigallocatechin-3-gallate (EGCG) in Detachment-induced Cell Death


Abstract
Adherent cells, such as those found in epithelial tissues, must be physically associated with extracellular matrix (ECM)components to survive. Though stimulation by growth factors is an essential factor in cell survival, normal cells also requires cell adhesion to ECM proteins. The cessation of these anchorage-mediated signals seems to be a common mechanism to physiologically terminate the life cycle of these cells by apoptosis. This form of cell death has been termed anoikis.In cancer, resistance to anoikis of cancer cell is important in invasion and metastasis. The present study investigated the intracellular mechanism involved in anoikis, especially in cells treated with epigallocatechin-3-gallate(EGCG). To induce anoikis, cell culture plates were coated with 10 §¶/ml poly-HEMA. A549 lung adenocarcinoma cells were grown in RPMI 1640 medium with/without 10% fetal bovine serum, and then cells were replated on cell culture dishes coated with poly-HEMA in the presence or absence of serum. On the other hand, EGFR inhibitor, PI3K inhibitor, and EGCG were treated to the anoikis status cells, in order to evaluate the factors of anoikis. The result revealed that growth factors or loss of adhesion can increase phosphorylate Akt. In addition, lack of cell adhesion fails to activate pro-apoptotic factors directly. Activity of Erk kinase depends on not only EGFR signaling but also cell adhesion. Akt activation is mainly affected by EGCG whereas Raf-1 activation is controlled by the presence of cell contact. In addition, EGCG increased the level of NFkB, whereas phophroylated PTEN and total PTEN were not different. In this report,increase of NFkB was correlated with Akt phosphorylation, suggesting that EGCG can protect cells from detachment?induced cell death through Akt activation and subsequent NFkB.
KEYWORD
Lung adenocarcinoma cells, EGCG, Akt, NFkB, Poly-HEMA.
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