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 language | English |
|---|---|
| Pages (from-to) | 823-828 |
| Number of pages | 6 |
| Journal | Oncology Reports |
| Volume | 17 |
| Issue number | 4 |
| Publication status | Published - Apr 2007 |
Fingerprint
Keywords
- Apoptosis
- Aspirin
- Celecoxib
- Chemoprevention
- Lung cancer
- NFκB
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Failure of apoptosis and activation on NFκB by celecoxib and aspirin in lung cancer cell lines
AU - Gradilone, Angela
AU - Silvestri, Ida
AU - Scarpa, Susanna
AU - Morrone, Stefania
AU - Gandini, Orietta
AU - Pulcinelli, Fabio M.
AU - Gianni, Walter
AU - Frati, Luigi
AU - Aglianò, Anna Maria
AU - Gazzaniga, Paola
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Aspirin
KW - Celecoxib
KW - Chemoprevention
KW - Lung cancer
KW - NFκB
UR - http://www.scopus.com/inward/record.url?scp=34249942270&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249942270&partnerID=8YFLogxK
M3 - Article
C2 - 17342322
AN - SCOPUS:34249942270
VL - 17
SP - 823
EP - 828
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 4
ER -