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.