SEARCH:   Advanced

Blood, 15 February 2005, Vol. 105, No. 4, pp. 1750-1758. Prepublished online as a Blood First Edition Paper on October 21, 2004; DOI 10.1182/blood-2004-04-1360. This Article Full Text (PDF) All Versions of this Article: 2004-04-1360v1 105/4/1750    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Piva, R. Articles by Santoro, M G Search for Related Content PubMed PubMed Citation Articles by Piva, R. Articles by Santoro, M G Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 8, 2004 Accepted October 12, 2004 15-Deoxy-12,14-prostaglandin J2 induces apoptosis in human malignant B-cells: an effect associated with inhibition of NF-B activity and down-regulation of anti-apoptotic proteins Roberto Piva, Patrizia Gianferretti, Alessandra Ciucci, Riccardo Taulli, Giuseppe Belardo, and M G Santoro* Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome, Italy; Department of Pathology and Center for Experimental Research and Medical Studies (CERMS), University of Turin, Turin, Italy Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome, Italy Department of Pathology and Center for Experimental Research and Medical Studies (CERMS), University of Turin, Turin, Italy * Corresponding author; email: santoro{at}bio.uniroma2.it. Cyclopentenone prostaglandins are potent inhibitors of NF-B, a transcription factor with a critical role in promoting inflammation and connected with multiple aspects of oncogenesis and cancer cell survival. In the present report we investigated the role of NF-B in the anti-neoplastic activity of the cyclopentenone prostaglandin 15-deoxy-12,14-PGJ2 (15d-PGJ2) in multiple myeloma (MM) and Burkitt's lymphoma (BL) cells expressing constitutively active NF-B. 15d-PGJ2 was found to suppress constitutive NF-B activity and potently induce apoptosis in both types of B-cell malignancies. 15d-PGJ2-Induced apoptosis occurs through multiple caspase activation pathways involving caspase-8 and caspase-9, and is prevented by pre-treatment with the pan-caspase inhibitor ZVAD. NF-B inhibition is accompanied by rapid down-regulation of NF-B-dependent anti-apoptotic gene products, including cIAP-1, cIAP-2, XIAP and cFLIP. These effects were mimicked by the proteasome inhibitor MG-132, but not by the peroxisome proliferator-activated receptor- (PPAR-) agonist troglitazone, suggesting that 15d-PGJ2-induced apoptosis is independent of PPAR-. Knockdown of the NF-B p65-subunit by lentiviral-mediated shRNA interference also resulted in apoptosis induction in malignant B cells with constitutively active NF-B. The results indicate that inhibition of NF-B plays a major role in the pro-apoptotic activity of 15d-PGJ2 in aggressive B-cell malignancies characterized by aberrant regulation of NF-B. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Piva, B. Ruggeri, M. Williams, G. Costa, I. Tamagno, D. Ferrero, V. Giai, M. Coscia, S. Peola, M. Massaia, et al. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib Blood, March 1, 2008; 111(5): 2765 - 2775. [Abstract] [Full Text] [PDF] C. Fionda, F. Nappi, M. Piccoli, L. Frati, A. Santoni, and M. Cippitelli Inhibition of Trail Gene Expression by Cyclopentenonic Prostaglandin 15-Deoxy-{Delta}12,14-Prostaglandin J2 in T Lymphocytes Mol. Pharmacol., November 1, 2007; 72(5): 1246 - 1257. [Abstract] [Full Text] [PDF] H. Hasegawa, Y. Yamada, K. Komiyama, M. Hayashi, M. Ishibashi, T. Sunazuka, T. Izuhara, K. Sugahara, K. Tsuruda, M. Masuda, et al. A novel natural compound, a cycloanthranilylproline derivative (Fuligocandin B), sensitizes leukemia cells to apoptosis induced by tumor necrosis factor related apoptosis-inducing ligand (TRAIL) through 15-deoxy-{Delta}12, 14 prostaglandin J2 production Blood, September 1, 2007; 110(5): 1664 - 1674. [Abstract] [Full Text] [PDF] J. J. Schlezinger, J. K. Emberley, S. L. Bissonnette, and D. H. Sherr An L-Tyrosine Derivative and PPAR{gamma} Agonist, GW7845, Activates a Multifaceted Caspase Cascade in Bone Marrow B Cells Toxicol. Sci., July 1, 2007; 98(1): 125 - 136. [Abstract] [Full Text] [PDF] C. Fionda, F. Nappi, M. Piccoli, L. Frati, A. Santoni, and M. Cippitelli 15-Deoxy-{Delta}12,14-Prostaglandin J2 Negatively Regulates rankl Gene Expression in Activated T Lymphocytes: Role of NF-{kappa}B and Early Growth Response Transcription Factors J. Immunol., April 1, 2007; 178(7): 4039 - 4050. [Abstract] [Full Text] [PDF] E. Caselli, S. Fiorentini, C. Amici, D. Di Luca, A. Caruso, and M. G. Santoro Human herpesvirus 8 acute infection of endothelial cells induces monocyte chemoattractant protein 1-dependent capillary-like structure formation: role of the IKK/NF-{kappa}B pathway Blood, April 1, 2007; 109(7): 2718 - 2726. [Abstract] [Full Text] [PDF] A. Ciucci, P. Gianferretti, R. Piva, T. Guyot, T. J. Snape, S. M. Roberts, and M. G. Santoro Induction of Apoptosis in Estrogen Receptor-Negative Breast Cancer Cells by Natural and Synthetic Cyclopentenones: Role of the I{kappa}B Kinase/Nuclear Factor-{kappa}B Pathway Mol. Pharmacol., November 1, 2006; 70(5): 1812 - 1821. [Abstract] [Full Text] [PDF] S.-H. Jo, C. Yang, Q. Miao, M. Marzec, M. A. Wasik, P. Lu, and Y. L. Wang Peroxisome Proliferator-Activated Receptor {gamma} Promotes Lymphocyte Survival through Its Actions on Cellular Metabolic Activities J. Immunol., September 15, 2006; 177(6): 3737 - 3745. [Abstract] [Full Text] [PDF] J. J. Schlezinger, J. K. Emberley, and D. H. Sherr Activation of Multiple Mitogen-Activated Protein Kinases in Pro/Pre-B Cells by GW7845, a Peroxisome Proliferator-Activated Receptor {gamma} Agonist, and Their Contribution to GW7845-Induced Apoptosis Toxicol. Sci., August 1, 2006; 92(2): 433 - 444. [Abstract] [Full Text] [PDF] S. Nakata, T. Yoshida, T. Shiraishi, M. Horinaka, J. Kouhara, M. Wakada, and T. Sakai 15-Deoxy-{Delta}12,14-prostaglandin J2 induces death receptor 5 expression through mRNA stabilization independently of PPAR{gamma} and potentiates TRAIL-induced apoptosis. Mol. Cancer Ther., July 1, 2006; 5(7): 1827 - 1835. [Abstract] [Full Text] [PDF] M. A. Peraza, A. D. Burdick, H. E. Marin, F. J. Gonzalez, and J. M. Peters The Toxicology of Ligands for Peroxisome Proliferator-Activated Receptors (PPAR) Toxicol. Sci., April 1, 2006; 90(2): 269 - 295. [Abstract] [Full Text] [PDF] H. Lu, W. Ouyang, and C. Huang Inflammation, a Key Event in Cancer Development Mol. Cancer Res., April 1, 2006; 4(4): 221 - 233. [Abstract] [Full Text] [PDF] T.-N. Lin, W.-M. Cheung, J.-S. Wu, J.-J. Chen, H. Lin, J.-J. Chen, J.-Y. Liou, S.-K. Shyue, and K. K. Wu 15d-Prostaglandin J2 Protects Brain From Ischemia-Reperfusion Injury Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 481 - 487. [Abstract] [Full Text] [PDF] R. Piva, R. Chiarle, A. D. Manazza, R. Taulli, W. Simmons, C. Ambrogio, V. D'Escamard, E. Pellegrino, C. Ponzetto, G. Palestro, et al. Ablation of oncogenic ALK is a viable therapeutic approach for anaplastic large-cell lymphomas Blood, January 15, 2006; 107(2): 689 - 697. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020