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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 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 Citation Map 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. Related Collections Apoptosis Signal Transduction Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 antiapoptotic proteins Roberto Piva, Patrizia Gianferretti, Alessandra Ciucci, Riccardo Taulli, Giuseppe Belardo, and M. Gabriella Santoro From the Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome, Italy; and the Department of Pathology and Center for Experimental Research and Medical Studies (CERMS), University of Turin, Turin, Italy. Cyclopentenone prostaglandins are potent inhibitors of nuclear factor-B (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 antineoplastic activity of the cyclopentenone prostaglandin 15-deoxy-12,14-PGJ2 (15d-PGJ2) in multiple myeloma (MM) and Burkitt 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 pretreatment with the pan-caspase inhibitor ZVAD (z-Val-Ala-Asp). NF-B inhibition is accompanied by rapid down-regulation of NF-B-dependent antiapoptotic gene products, including cellular inhibitor-of-apoptosis protein 1 (cIAP-1), cIAP-2, X-chromosome-linked inhibitor-of-apoptosis protein (XIAP), and FLICE-inhibitory protein (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 proapoptotic activity of 15d-PGJ2 in aggressive B-cell malignancies characterized by aberrant regulation of NF-B. (Blood. 2005;105:1750-1758) 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. 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