title: Celecoxib prevents curcumin-induced apoptosis in a hematopoietic cancer cell model.
abstract: Molecules targeting pro-inflammatory pathways have demonstrated beneficial effects in cancer treatment. More recently, combination of natural and synthetic anti-inflammatory drugs was suggested as an appealing strategy to inhibit tumor growth. Herein, we show that curcumin, a polyphenol from Curcuma longa and celecoxib induce apoptosis in hematopoietic cancer cell lines (Hel, Jurkat, K562, Raji, and U937). Further investigations on the most sensitive cell line, U937, indicated that these effects were tightly associated with an accumulation of the cells in S and G2/M for curcumin and in G0/G1 phase of cell cycle for celecoxib, respectively. The effect of celecoxib on cell cycle is associated with an induction of p27 and the down-regulation of cyclin D1. However, in the case of combination experiments, the pretreatment of U937 cells with celecoxib at non-apoptogenic concentrations counteracted curcumin-induced apoptosis. We found that this effect correlated with the prevention of the accumulation in S and G2/M phase of cell cycle induced by curcumin. Similar results have been obtained when celecoxib and curcumin were co-administrated at the same time. Overall our data suggest that this natural and synthetic drug combination is detrimental for cell death induction.
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, Luxembourg, Luxembourg.
authors.forename: Cyril
authors.initials: C
authors.lastname: Sobolewski
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, Luxembourg, Luxembourg.
authors.forename: Florian
authors.initials: F
authors.lastname: Muller
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, Luxembourg, Luxembourg.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cerella
authors.affiliation: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, Luxembourg, Luxembourg.
authors.forename: Mario
authors.initials: M
authors.lastname: Dicato
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D000068579:Celecoxib / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D019938:Cyclin D1 / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D020298:U937 Cells
chemical_list: D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003474:Curcumin; D000068579:Celecoxib
keywords: COX-2; apoptosis; celecoxib; cell cycle; curcumin