Sulindac enhances tumor necrosis factor-α-mediated apoptosis of lung cancer cell lines by inhibition of nuclear factor-κB

Kevin S. Berman, Udit N. Verma, Gwyndolen Harburg, John D. Minna, Melanie H. Cobb, Richard B. Gaynor

Research output: Contribution to journalArticle

62 Scopus citations


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 languageEnglish (US)
Pages (from-to)354-360
Number of pages7
JournalClinical Cancer Research
Issue number2
StatePublished - Mar 14 2002


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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