Inhibition of arsenite-induced apoptosis and AP-1 activity by epigallocatechin-3-gallate and theaflavins.
Arsenite-induced apoptosis appears to be important in its toxicity and its role in carcinogenesis. Green tea has been used as a traditional Chinese remedy for detoxification of arsenite-caused toxicity. In the present work, we found that tea polyphenols, EGCG and theaflavins, effectively blocked arsenite-induced apoptosis of JB6 cells and inhibited arsenite-induced AP-1 transcription activity and AP-1 DNA binding activity. EGCG and theaflavins potently inhibited arsenite-induced Erks activity, but not p38 kinase activity. PD 98059, an inhibitor of Erks, and DNM-JNK1 blocked arsenite-induced apoptosis, while SB202190, an inhibitor of p38 kinases, or DNM-p38 kinase did not. We conclude that Erks and JNKs may be involved in arsenite-induced apoptosis, and the inhibition of arsenite-induced apoptosis by EGCG and theaflavins may be mediated by a decreased phosphorylation of Erks and JNKs. Furthermore, these results provide a possible mechanism for the detoxification effect of tea on arsenite-induced toxicity.
Chen
N Y
NY
The Hormel Institute, University of Minnesota, Austin 55912, USA.
Ma
W Y
WY
Yang
C S
CS
Dong
Z
Z
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000037:antagonists & inhibitors* / Q000633:toxicity; D044946:Biflavonoids; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004347:Drug Interactions; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D010766:Phosphorylation; D011108:Polymers / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013662:Tea; D013723:Teratogens / Q000633:toxicity*; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D016587:Antimutagenic Agents; D000975:Antioxidants; D018053:Arsenites; D044946:Biflavonoids; D005419:Flavonoids; D007093:Imidazoles; D010636:Phenols; D011108:Polymers; D011725:Pyridines; D013662:Tea; D013723:Teratogens; D018808:Transcription Factor AP-1; C056068:theaflavin; D002392:Catechin; D004247:DNA; C045651:epigallocatechin gallate; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C015001:arsenite; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one