Arsenic hexoxide (
As4O6) has been used in Korean
folk remedy for the treatment of
cancer since the late 1980s. Evidence suggests that the anticancer effects of
As4O6 are different from those of
As2O3.
Tumor necrosis factor-α (TNF-α) is generally increased in advanced
cancer and is closely related to
cancer progression, although it has
cancer-killing effects. The reason is that TNF-α activates nuclear factor-κB (NF-κB) that is involved in cell proliferation, invasion, drug resistance and
metastasis. In the present study, we investigated the effects of
As4O6 on NF-κB activity, NF-κB-mediated cellular responses, and NF-κB-regulated gene expressions involved in
metastasis at the concentrations of
As4O6 where no cytotoxicity was observed.
As4O6 suppressed NF-κB activation in both TNF-α-treated and control cells, and also suppressed IκB phosphorylation in a time-dependent manner, suggesting the suppression of NF-κB results, in part, from the inhibition of IκB degradation. We also confirmed the anti-NF-κB activity of
As4O6 with synergism with TNF-α by augmenting
caspase-8 activation.
As4O6 also suppressed NF-κB activation induced by TNF-α, and some of the downstream NF-κB-regulated
proteins involved in
cancer proliferation, anti-apoptosis and
metastasis. In conclusion, the present study demonstrated that
As4O6 has anticancer properties by inhibiting NF-κB activation and NF-κB-regulated
proteins at least in part through the inhibition of IκB phosphorylation, especially in the conditions of advanced
cancer where TNF-α is highly secreted.