Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Aspirin/pharmacology , Colorectal Neoplasms/prevention & control , NF-kappa B/antagonists & inhibitors , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/therapeutic use , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/pharmacology , Humans , Isoenzymes/antagonists & inhibitors , Membrane Proteins , Prostaglandin-Endoperoxide SynthasesABSTRACT
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)-kappaB, 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)-alpha-mediated NF-kappaB activation. Here, we demonstrate that treatment of the non-small cell lung carcinoma cells NCI-H157 and NCI-H1299 with sulindac greatly enhances TNF-alpha-mediated apoptosis. We further show that sulindac inhibits TNF-alpha-mediated activation of NF-kappaB DNA binding and nuclear translocation of NF-kappaB. These results suggest that sulindac and other nonsteroidal anti-inflammatory drug inhibitors of NF-kappaB activation may serve as useful agents in cancer chemotherapy.
