title: Therapeutic dosages of aspirin counteract the IL-6 induced pro-tumorigenic effects by slowing down the ribosome biogenesis rate.
abstract: Chronic inflammation is a risk factor for the onset of cancer and the regular use of aspirin reduces the risk of cancer development. Here we showed that therapeutic dosages of aspirin counteract the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6 in cancer and non-cancer cell lines, and in mouse liver in vivo. We found that therapeutic dosages of aspirin prevented IL-6 from inducing the down-regulation of p53 expression and the acquisition of the epithelial mesenchymal transition (EMT) phenotypic changes in the cell lines. This was the result of a reduction in c-Myc mRNA transcription which was responsible for a down-regulation of the ribosomal protein S6 expression which, in turn, slowed down the rRNA maturation process, thus reducing the ribosome biogenesis rate. The perturbation of ribosome biogenesis hindered the Mdm2-mediated proteasomal degradation of p53, throughout the ribosomal protein-Mdm2-p53 pathway. P53 stabilization hindered the IL-6 induction of the EMT changes. The same effects were observed in livers from mice stimulated with IL-6 and treated with aspirin. It is worth noting that aspirin down-regulated ribosome biogenesis, stabilized p53 and up-regulated E-cadherin expression in unstimulated control cells also. In conclusion, these data showed that therapeutic dosages of aspirin increase the p53-mediated tumor-suppressor activity of the cells thus being in this way able to reduce the risk of cancer onset, either or not linked to chronic inflammatory processes.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Brighenti
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy.|Biomedical and Applied Research Center, University Hospital of Bologna, Policlinico S. Orsola-Malpighi, Bologna 40138, Italy.
authors.forename: Ferdinando Antonino
authors.initials: FA
authors.lastname: Giannone
authors.affiliation: Biomedical and Applied Research Center, University Hospital of Bologna, Policlinico S. Orsola-Malpighi, Bologna 40138, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fornari
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Onofrillo
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Govoni
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Montanaro
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Treré
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Derenzini
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D012318:RNA Polymerase I / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015850:Interleukin-6; D016271:Proto-Oncogene Proteins c-myc; D012335:RNA, Ribosomal; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D012318:RNA Polymerase I; D001241:Aspirin
keywords: aspirin; cancer; inflammation; p53; ribosome biogenesis