Celecoxib induces anoikis in human colon carcinoma cells associated with the deregulation of focal adhesions and nuclear translocation of p130Cas

dc.creatorCasanova, Isolda
dc.creatorParreño, Matilde
dc.creatorFarré, Maria Lourdes Vallve
dc.creatorGuerrero, Sílvia
dc.creatorCéspedes, M Virtudes
dc.creatorPavon, Miguel Angel
dc.creatorSancho, Francesc J
dc.creatorMarcuello, Eugenio
dc.creatorTrias, Manuel
dc.creatorMangues, Ramon
dc.date2017-05-29T14:16:25Z
dc.date2017-05-29T14:16:25Z
dc.date2006
dc.date.accessioned2023-09-26T22:43:21Z
dc.date.available2023-09-26T22:43:21Z
dc.identifierCASANOVA, I. et al. Celecoxib induces anoikis in human colon carcinoma cells associated with the deregulation of focal adhesions and nuclear translocation of p130Cas. International Journal of Cancer, v. 118, p. 2381–2389, 2006.
dc.identifier0020-7136
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/19033
dc.identifier10.1002/ijc.21662
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8882377
dc.descriptionFarre, Maria Lourdes Vallve “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.
dc.descriptionGrant sponsor: The Spanish Government; Grant numbers: SAF03/07437, FIS 01/0853, FISC03/10; Grant sponsor: Spanish National Health System; Grant numbers: FIS 98/3197, FIS 01/3085
dc.descriptionCelecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is effective as chemopreventive against colon cancer and it is the only nonsteoroidal antiinflammatory drug approved by the FDA for adjuvant therapy in patients with familial adenomatous polyposis. It is also being evaluated, within Phase II and III clinical trials, in combination with standard chemotherapy to treat sporadic colorectal cancer. Nevertheless, its antitumor mechanism of action is still not fully understood. In this study, we have evaluated the in vitro growth inhibitory effect of celecoxib in colon carcinoma cells and analyzed its mechanism of action. We report that the deregulation of the focal adhesion assembly protein Crk-associated substrate 130 kDa (p130Cas) by celecoxib plays a relevant role in the cytotoxic effect of this drug. Thus, celecoxib induces the proteolysis of p130Cas and the nuclear translocation of the 31 kDa generated fragment leading to apoptosis. Furthermore, overexpression of wild-type p130Cas reverts, in part, the growth inhibitory effect of celecoxib. In contrast, FAK and AKT do not appear to be involved in this activity. Our data suggest, for the first time, that the antitumor mechanism of action of celecoxib includes the induction of anoikis, an effect that is not related to COX-2 inhibition. Besides providing new insights into the antitumor effect of celecoxib, this novel mechanism of action holds potential relevance in drug development. Indeed, our results open the possibility to develop new celecoxib derivatives that induce anoikis without COX-2 inhibition so as to avoid the cardiovascular toxicity recently described for the COX-2 inhibitors.
dc.formatapplication/pdf
dc.languageeng
dc.publisherWiley
dc.rightsopen access
dc.subjectAnoikis
dc.subjectCelecoxib
dc.subjectp130Cas
dc.subjectCinase de adesão focal
dc.subjectCancer colorretal
dc.subjectAnoikis
dc.subjectCelecoxib
dc.subjectp130Cas
dc.subjectFocal adhesion kinase
dc.subjectColorectal cancer
dc.subjectAnoikis
dc.subjectCelecoxib
dc.subjectCancer colorretal
dc.titleCelecoxib induces anoikis in human colon carcinoma cells associated with the deregulation of focal adhesions and nuclear translocation of p130Cas
dc.typeArticle


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