Hayakawa S, Saeki K, Sazuka M, Suzuki Y, Shoji Y, Ohta T, Kaji K, Yuo A, Isemura M
School of Food and Nutritional Sciences, University of Shizuoka, Yada, Shizuoka, 422-8526, Japan.
Biochem Biophys Res Commun. 2001 Aug 3;285(5):1102-6. doi: 10.1006/bbrc.2001.5293.
Epigallocatechin gallate (EGCG) is known to induce apoptosis in various types of tumor cells, but the precise mechanism by which EGCG induces apoptosis remains to be elucidated. The Fas-Fas ligand system is one of the major pathways operating in the apoptotic cascade. The aim of this study was to examine the possibility that EGCG-binding to Fas triggers the Fas-mediated apoptosis. The EGCG treatment of human monocytic leukemia U937 cells resulted in elevation of caspase 8 activity and fragmentation of caspase 8. The DNA ladder formation caused by the EGCG treatment was inhibited by the caspase 8 inhibitor. These findings suggested the involvement of the Fas-mediated cascade in the EGCG-induced apoptosis in U937 cells. Affinity chromatography revealed the binding between EGCG and Fas. Thus, the results suggest that EGCG-binding to Fas, presumably on the cell surface, triggers the Fas-mediated apoptosis in U937 cells.
表没食子儿茶素没食子酸酯(EGCG)已知可诱导多种类型肿瘤细胞凋亡,但其诱导凋亡的确切机制仍有待阐明。Fas-Fas配体系统是凋亡级联反应中的主要途径之一。本研究的目的是探讨EGCG与Fas结合触发Fas介导凋亡的可能性。用EGCG处理人单核细胞白血病U937细胞导致半胱天冬酶8活性升高和半胱天冬酶8裂解。EGCG处理引起的DNA梯状条带形成被半胱天冬酶8抑制剂抑制。这些发现提示Fas介导的级联反应参与了EGCG诱导的U937细胞凋亡。亲和层析显示EGCG与Fas之间存在结合。因此,结果表明EGCG与可能位于细胞表面的Fas结合,触发了U937细胞中Fas介导的凋亡。