Sulindac Enhances the Killing of Cancer Cells Exposed to Oxidative Stress |
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| Authors: | Maria Marchetti Lionel Resnick Edna Gamliel Shailaja Kesaraju Herbert Weissbach David Binninger |
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| Affiliation: | 1. Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida, United States of America.; 2. Center for Molecular Biology and Biotechnology, Florida Atlantic University, Boca Raton, Florida, United States of America.;Bauer Research Foundation, United States of America |
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| Abstract: | BackgroundSulindac is an FDA-approved non-steroidal anti-inflammatory drug (NSAID) that affects prostaglandin production by inhibiting cyclooxygenases (COX) 1 and 2. Sulindac has also been of interest for more than decade as a chemopreventive for adenomatous colorectal polyps and colon cancer.Principal FindingsPretreatment of human colon and lung cancer cells with sulindac enhances killing by an oxidizing agent such as tert-butyl hydroperoxide (TBHP) or hydrogen peroxide. This effect does not involve cyclooxygenase (COX) inhibition. However, under the conditions used, there is a significant increase in reactive oxygen species (ROS) within the cancer cells and a loss of mitochondrial membrane potential, suggesting that cell death is due to apoptosis, which was confirmed by Tunel assay. In contrast, this enhanced killing was not observed with normal lung or colon cells.SignificanceThese results indicate that normal and cancer cells handle oxidative stress in different ways and sulindac can enhance this difference. The combination of sulindac and an oxidizing agent could have therapeutic value. |
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