To study whether the apoptotic effect of arsenic trioxide (As2O3) on colon cancer cells could be enhanced by the addition of sulindac, HCT116 cells were treated with As2O3 (1, 5, 10 µM) and sulindac (0.5 mM), either alone or in combination. As2O3 alone slightly inhibited the growth of HCT116 cells, whereas the combination of As2O3 and sulindac reduced cell growth by 30-40%. Annexin V staining indicated that the synergistic effect of the combination was mediated through increased apoptosis. We examined whether the combination of As2O3 and sulindac on apoptosis is mediated by inhibition of the NF-κB pathway in HCT116 colon cancer cells. Western blot analysis showed that the level of nuclear NF-κB (p65) was not changed significantly by As2O3 or sulindac treatment alone, while the level of nuclear NF-κB (p65) was drastically decreased in the combination treatment by inhibiting the phosphorylation and the degradation of IκB-α. These results suggest that sulindac enhances apoptosis when combined with As2O3 by inhibiting NF-κB activation mediated through the blocking of phosphorylation and degradation of IκB-α.

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