Recent studies have demonstrated that antineoplastic activity of Cox-2 inhibitors may depend on targets other than Cox: among those, nuclear factor kappa B (NF kappa B) 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 NF kappa B 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 NF kappa B 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 NF kappa B activation, with increased expression of NF kappa B-dependent genes, such as bcl-2, bcl-X-L and survivin. Similarly, aspirin at both concentrations did not induce any apoptotic response, but activated NF kappa B in a dose-dependent manner. This study supports the hypothesis that NF kappa B 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.
Failure of apoptosis and activation on NF kappa B by celecoxib and aspirin in lung cancer cell lines / Gradilone, Angela; Silvestri, Ida; Scarpa, Susanna; Morrone, Stefania; Gandini, Orietta; Pulcinelli, FABIO MARIA; Gianni, W; Frati, Luigi; Agliano', Anna Maria; Gazzaniga, Paola. - In: ONCOLOGY REPORTS. - ISSN 1021-335X. - STAMPA. - 17(4):(2007), pp. 823-828.
Failure of apoptosis and activation on NF kappa B by celecoxib and aspirin in lung cancer cell lines
GRADILONE, Angela;SILVESTRI, Ida;SCARPA, Susanna;MORRONE, Stefania;GANDINI, Orietta;PULCINELLI, FABIO MARIA;FRATI, Luigi;AGLIANO', Anna Maria;GAZZANIGA, PAOLA
2007
Abstract
Recent studies have demonstrated that antineoplastic activity of Cox-2 inhibitors may depend on targets other than Cox: among those, nuclear factor kappa B (NF kappa B) 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 NF kappa B 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 NF kappa B 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 NF kappa B activation, with increased expression of NF kappa B-dependent genes, such as bcl-2, bcl-X-L and survivin. Similarly, aspirin at both concentrations did not induce any apoptotic response, but activated NF kappa B in a dose-dependent manner. This study supports the hypothesis that NF kappa B 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.