Failure of apoptosis and activation on NFκB by celecoxib and aspirin in lung cancer cell lines

Angela Gradilone, Ida Silvestri, Susanna Scarpa, Stefania Morrone, Orietta Gandini, Fabio M. Pulcinelli, Walter Gianni, Luigi Frati, Anna Maria Aglianò, Paola Gazzaniga

Research output: Contribution to journalArticle

Abstract

Recent studies have demonstrated that antineoplastic activity of Cox-2 inhibitors may depend on targets other than Cox: among those, nuclear factor κB (NFκB) seems the most promising. Although preclinical studies have suggested that aspirin and Cox-2 inhibitors may influence the progression of lung cancer, the molecular mechanisms of these protective effects in this tumor type has not been fully elucidated. We investigated the effects of celecoxib and aspirin in the induction of apoptosis and in the ability to activate NFκB in three non-small cell lung cancer cell lines. Apoptosis was evaluated by FACS, caspase activation assay and expression of apoptosis-related genes by RT-PCR, while NFκB activation was assessed by immunofluorescence. No apoptotic response was observed after treatment with both high and low dose of celecoxib. Nevertheless, celecoxib at both concentrations induced a strong NFκB activation, with increased expression of NFκB-dependent genes, such as bcl-2, bcl-XL and survivin. Similarly, aspirin at both concentrations did not induce any apoptotic response, but activated NFκB in a dose-dependent manner. This study supports the hypothesis that NFκB activation is an important effect of NSAIDs in lung cancer, leading to apoptosis resistance. This effect of both aspirin and celecoxib may be considered undesirable in lung cancer chemoprevention.

Original languageEnglish
Pages (from-to)823-828
Number of pages6
JournalOncology Reports
Volume17
Issue number4
Publication statusPublished - Apr 2007

Fingerprint

Celecoxib
Aspirin
Lung Neoplasms
Apoptosis
Cell Line
Chemoprevention
Non-Steroidal Anti-Inflammatory Agents
Caspases
Non-Small Cell Lung Carcinoma
Antineoplastic Agents
Genes
Fluorescent Antibody Technique
Polymerase Chain Reaction

Keywords

  • Apoptosis
  • Aspirin
  • Celecoxib
  • Chemoprevention
  • Lung cancer
  • NFκB

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gradilone, A., Silvestri, I., Scarpa, S., Morrone, S., Gandini, O., Pulcinelli, F. M., ... Gazzaniga, P. (2007). Failure of apoptosis and activation on NFκB by celecoxib and aspirin in lung cancer cell lines. Oncology Reports, 17(4), 823-828.

Failure of apoptosis and activation on NFκB by celecoxib and aspirin in lung cancer cell lines. / Gradilone, Angela; Silvestri, Ida; Scarpa, Susanna; Morrone, Stefania; Gandini, Orietta; Pulcinelli, Fabio M.; Gianni, Walter; Frati, Luigi; Aglianò, Anna Maria; Gazzaniga, Paola.

In: Oncology Reports, Vol. 17, No. 4, 04.2007, p. 823-828.

Research output: Contribution to journalArticle

Gradilone, A, Silvestri, I, Scarpa, S, Morrone, S, Gandini, O, Pulcinelli, FM, Gianni, W, Frati, L, Aglianò, AM & Gazzaniga, P 2007, 'Failure of apoptosis and activation on NFκB by celecoxib and aspirin in lung cancer cell lines', Oncology Reports, vol. 17, no. 4, pp. 823-828.
Gradilone A, Silvestri I, Scarpa S, Morrone S, Gandini O, Pulcinelli FM et al. Failure of apoptosis and activation on NFκB by celecoxib and aspirin in lung cancer cell lines. Oncology Reports. 2007 Apr;17(4):823-828.
Gradilone, Angela ; Silvestri, Ida ; Scarpa, Susanna ; Morrone, Stefania ; Gandini, Orietta ; Pulcinelli, Fabio M. ; Gianni, Walter ; Frati, Luigi ; Aglianò, Anna Maria ; Gazzaniga, Paola. / Failure of apoptosis and activation on NFκB by celecoxib and aspirin in lung cancer cell lines. In: Oncology Reports. 2007 ; Vol. 17, No. 4. pp. 823-828.
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