Arsenite has a long history in treating
leukemia, which might be also effective in the
therapy of other
cancers. Our previous published data have demonstrated that
arsenite exposure induces apoptosis in the HepG2 human
hepatoma cells via activating JNKs/AP-1 pathway, but the upstream signaling events responsible for JNKs (
c-Jun N-terminal kinase) cascade activation have not been fully discovered. Since cross-talk between IKK/NF-κB and JNKs pathways under stress conditions is a hot topic, in this article, we investigate the potential roles of IKKα and IKKβ, the catalytic subunits of IKK complexes, in the
arsenite-induced JNKs pathway activation in the HepG2 cells. We found that
arsenite exposure induced JNKs and
AP-1 activation accompanying with a significant reduction of both IKKα and IKKβ expressions. Overexpression of IKKβ, but not of IKKα, inhibited
arsenite-induced MKK7/JNKs/AP-1 pathway activation as well as the apoptotic response. Therefore, we conclude that the downregulation of IKKβ expression is the prerequisite signaling event for mediating JNKs pathway activation and the cellular apoptotic response in the HepG2 cells under
arsenite exposure. Targeting IKKβ might be helpful to enhance the
tumor therapeutic effect of
arsenite.