Apoptosis induction by epigallocatechin gallate involves its binding to Fas.
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.
Hayakawa
S
S
School of Food and Nutritional Sciences, University of Shizuoka, Yada, Shizuoka, 422-8526, Japan.
Saeki
K
K
Sazuka
M
M
Suzuki
Y
Y
Shoji
Y
Y
Ohta
T
T
Kaji
K
K
Yuo
A
A
Isemura
M
M
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D002846:Chromatography, Affinity; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D020298:U937 Cells; D019014:fas Receptor / Q000378:metabolism*
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D019014:fas Receptor; D002392:Catechin; C045651:epigallocatechin gallate; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases