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Sulindac enhances arsenic trioxide-mediated apoptosis by inhibition of NF-κB in HCT116 colon cancer cells

Sulindac enhances arsenic trioxide-mediated apoptosis by inhibition of NF-κB in HCT116 colon... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Oncology Reports Spandidos Publications

Sulindac enhances arsenic trioxide-mediated apoptosis by inhibition of NF-κB in HCT116 colon cancer cells

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Publisher
Spandidos Publications
Copyright
Copyright © Spandidos Publications
ISSN
1021-335X
eISSN
1791-2431
DOI
10.3892/or.20.1.41
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Oncology ReportsSpandidos Publications

Published: Jul 1, 2008

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