Sulindac enhances the killing of cancer cells exposed to oxidative stress.
BACKGROUND
Sulindac 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.


RESULTS
Pretreatment 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.


CONCLUSIONS
These 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.
Marchetti
Maria
M
Center for Molecular Biology and Biotechnology, Florida Atlantic University, Boca Raton, Florida, United States of America.
Resnick
Lionel
L
Gamliel
Edna
E
Kesaraju
Shailaja
S
Weissbach
Herbert
H
Binninger
David
D
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D013467:Sulindac / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D017382:Reactive Oxygen Species; D013467:Sulindac