Green tea catechin controls apoptosis in colon cancer cells by attenuation of H2O2-stimulated COX-2 expression via the AMPK signaling pathway at low-dose H2O2.
This study investigated the apoptotic regulation by green tea catechin epigallcatechin-3-gallate (EGCG) on colon cancer cells in the presence of low-dose H(2)O(2) known to exert the activation of signal pathways leading to cell proliferation. In the presence of low-dose H(2)O(2), EGCG induced apoptosis and abolished the cell-proliferative effect exhibited by low-dose H(2)O(2). This reduction of growth was accompanied by an activation of AMP-activated kinase (AMPK), a decrease in cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) levels, and the induction of apoptotic markers such as p53 and poly(ADP-ribose) polymerase (PARP) cleavage. The low-dose H(2)O(2) stimulated COX-2 expression, and treating cells with synthetic AMPK activator AICAR (5-aminoimiazole-4-carboxamide-1-beta-d-ribofuranoside) resulted in greater suppression of COX-2 expression and PGE(2). By treating cells with high concentrations of the reactive oxygen species (ROS) scavenger NAC (N-acetyl-1-cysteine), the apoptotic effect of EGCG was abolished and led to suppression of AMPK and COX-2, indicating that the liberation of excessive ROS might be the upstream signal of the AMPK-COX-2 signaling pathway even in the presence of low-dose H(2)O(2).
Park
In-Ja
IJ
Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species, Kyung Hee University College of Medicine, Seoul, Korea.
Lee
Yun-Kyoung
YK
Hwang
Jin-Taek
JT
Kwon
Dae-Young
DY
Ha
Joohun
J
Park
Ock Jin
OJ
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000111:Acetylcysteine / Q000494:pharmacology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013662:Tea / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016166:Free Radical Scavengers; D016877:Oxidants; D017382:Reactive Oxygen Species; D012265:Ribonucleotides; D013662:Tea; D016159:Tumor Suppressor Protein p53; D000620:Aminoimidazole Carboxamide; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011065:Poly(ADP-ribose) Polymerases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D015232:Dinoprostone; D000111:Acetylcysteine