Novel combination of celecoxib and proteasome inhibitor MG132 provides synergistic antiproliferative and proapoptotic effects in human liver tumor cells. Cell Cycle. (Articolo in rivista)

Type
Label
  • Novel combination of celecoxib and proteasome inhibitor MG132 provides synergistic antiproliferative and proapoptotic effects in human liver tumor cells. Cell Cycle. (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Alternative label
  • Cusimano A, Azzolina A, Iovanna JL, Bachvarov D, McCubrey JA, D'Alessandro N, Montalto G, Cervello M. (2010)
    Novel combination of celecoxib and proteasome inhibitor MG132 provides synergistic antiproliferative and proapoptotic effects in human liver tumor cells. Cell Cycle.
    in Cell cycle (Georget. Tex.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Cusimano A, Azzolina A, Iovanna JL, Bachvarov D, McCubrey JA, D'Alessandro N, Montalto G, Cervello M. (literal)
Pagina inizio
  • 1399 (literal)
Pagina fine
  • 1410 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 9 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#note
  • PubMed PMID: 20305374. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 11 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 7 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Institute of Biomedicine and Molecular Immunology \"Alberto Monroy\"; National Research Council (CNR); Palermo, Italy; Institut National de la Santé et de la Recherche Médicale (INSERM); U624 Stress Cellulaire; Marseilles, France; Cancer Research Centre; Hôpital L'Hotel-Dieu de Québec; Centre Hospitalier Universitaire de Québec; Québec (Québec), Canada; Department of Molecular Medicine; Faculty of Medicine; Laval University; Québec (Québec), Canada; 5Department of Microbiology and Immunology; Brody School of Medicine at East Carolina University; Greenville, NC USA; Department of Pharmacological Sciences \"Pietro Benigno\"; Department of Clinical Medicine and Emergency Pathologies; University of Palermo; Palermo, Italy (literal)
Titolo
  • Novel combination of celecoxib and proteasome inhibitor MG132 provides synergistic antiproliferative and proapoptotic effects in human liver tumor cells. Cell Cycle. (literal)
Abstract
  • Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Celecoxib (Celebrex®) exhibits antitumor effects in human HCC cells, and its mechanism of action is mediated either by its ability to inhibit cyclooxygenase 2 (COX-2) or by a number of various other COX-2 independent effects. Proteasome inhibitors (PIs) can exert cell growth inhibitory and apoptotic effects in different tumor cell types, including HCC cells. The present study examined the interaction between celecoxib and the PI MG132 in two human liver tumor cell lines HepG2 and HA22T/VGH. Our data showed that each inhibitor reduced proliferation and induced apoptosis in a dose-dependent manner in both cell lines. Moreover, the combination of celecoxib with MG132 synergistically inhibited cell viability and increased apoptosis, as documented by caspase 3 and 7 activation, PARP cleavage, and downregulation of Bcl-2. Celecoxib and MG132, both alone and synergistically in combination, induced expression of the endoplasmic reticulum (ER) stress genes ATF4, CHOP, TRB3 and promoted the splicing of XBP1 mRNA. Knockdown of TRB3 mRNA expression by small interference RNA significantly decreased combination-induced cell death in HA22T/VGH cells, whereas it increased combination-induced cell death in HepG2 cells, suggesting that activation of the ER stress response might have either a detrimental or a protective role in liver tumor cell survival. In conclusion, our data indicate that combination treatment with celecoxib and MG132 resulted in synergistic antiproliferative and proapoptotic effects against liver cancer cells, providing a rational basis for the clinical use of this combination in the treatment of liver cancer. (literal)
Prodotto di
Autore CNR

Incoming links:


Autore CNR di
Prodotto
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
data.CNR.it