Programmed cell death (apoptosis) is induced by certain anticancer therapies, and resistance to apoptosis is a major mechanism by which tumors evade these therapies. The transcription factor nuclear factor (NF)-κB, which is frequently activated by treatment of cancer cells with different chemotherapeutic agents, promotes cell survival, whereas its inhibition leads to enhanced apoptosis. Recently, sulindac and other nonsteroidal anti-inflammatory drugs have been shown to inhibit tumor necrosis factor (TNF)-α-mediated NF-κB activation. Here, we demonstrate that treatment of the non-small cell lung carcinoma cells NCI-H157 and NCI-H1299 with sulindac greatly enhances TNF-α-mediated apoptosis. We further show that sulindac inhibits TNF-α-mediated activation of NF-κB DNA binding and nuclear translocation of NF-κB. These results suggest that sulindac and other nonsteroidal anti-inflammatory drug inhibitors of NF-κB activation may serve as useful agents in cancer chemotherapy.
|Original language||English (US)|
|Number of pages||7|
|Journal||Clinical Cancer Research|
|State||Published - 2002|
ASJC Scopus subject areas
- Cancer Research