title: COX-2-dependent and COX-2-independent mode of action of celecoxib in human liver cancer cells.
abstract: Celecoxib (Celebrex((R)), Pfizer) is a selective cyclooxygenase-2 (COX-2) inhibitor with chemopreventive and antitumor effects. However, it is now well known that celecoxib has several COX-2-independent activities. To better understand COX-2-independent molecular mechanisms underlying the antitumor activity of celecoxib, we investigated the expression profile of the celecoxib-treated COX-2-positive (Huh7) and COX-2-negative (HepG2) liver cancer cell lines, using microarray analysis. Celecoxib treatment resulted in significantly altered expression levels of 240 and 403 transcripts in Huh7 and HepG2 cells, respectively. Confirmation of the microarray results was performed for selected genes by semiquantitative RT-PCR. A pathway/functional analysis of celecoxib-affected transcripts, using ingenuity pathway analysis and exploring biological association networks, revealed that celecoxib modulates expression of numerous genes involved in a variety of cellular processes, including cell death, cellular growth and proliferation, lipid metabolism, and energy turnover. Some of these processes were common for both HCC cell lines and seem to be coupled with NF-κB signaling, while others were cell-specific and possibly linked to the presence or the absence of COX-2 activity in the corresponding cell line. Many novel genes emerged from our analyses that were not previously reported to be affected by celecoxib. Further studies on selected celecoxib-responsive genes will establish if they may serve as potential molecular targets for more effective therapeutic strategies in HCC.
authors.affiliation: Institute of Biomedicine and Molecular Immunology Alberto Monroy, National Research Council, Palermo, Italy.
authors.forename: Melchiorre
authors.initials: M
authors.lastname: Cervello
authors.forename: Dimcho
authors.initials: D
authors.lastname: Bachvarov
authors.forename: Antonella
authors.initials: A
authors.lastname: Cusimano
authors.forename: Francesca
authors.initials: F
authors.lastname: Sardina
authors.forename: Antonina
authors.initials: A
authors.lastname: Azzolina
authors.forename: Nadia
authors.initials: N
authors.lastname: Lampiasi
authors.forename: Lydia
authors.initials: L
authors.lastname: Giannitrapani
authors.forename: James A
authors.initials: JA
authors.lastname: McCubrey
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montalto
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D015398:Signal Transduction / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib