Sulindac Enhances Tumor Necrosis Factor-α-mediated Apoptosis of Lung Cancer Cell Lines by Inhibition of Nuclear Factor-κB

• Published in: Clinical cancer research Vol. 8; no. 2; pp. 354 - 360
• Main Authors: BERMAN, Kevin S, VERMA, Udit N, HARBURG, Gwyndolen, MINNA, John D, COBB, Melanie H, GAYNOR, Richard B
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-02-2002
• Subjects: Antineoplastic agents; Biological and medical sciences; Chemotherapy; Medical sciences; Pharmacology. Drug treatments; Antineoplastic agent; Human; Lung disease; Respiratory disease; Malignant tumor; Acetic acid derivative; In vitro; Biological activity; Bronchopulmonary; Non steroidal antiinflammatory agent; Cell death; Sulindac; Established cell line; Bronchus disease; Indene derivatives; Transcription factor NFκB; Mechanism of action; Tumor cell; Tumor necrosis factor α; Apoptosis; Non small cell carcinoma
• ISSN: 1078-0432; 1557-3265

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.