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Blood, 1 January 2004, Vol. 103, No. 1, pp. 194-207. Prepublished online as a Blood First Edition Paper on September 4, 2003; DOI 10.1182/blood-2003-05-1577. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1577v1 103/1/194    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 Garattini, E. Articles by Pisano, C. Search for Related Content PubMed PubMed Citation Articles by Garattini, E. Articles by Pisano, C. Related Collections Neoplasia Apoptosis Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis Enrico Garattini, Edoardo Parrella, Luisa Diomede, Maurizio Gianni', Yesim Kalac, Lucio Merlini, Daniele Simoni, Romina Zanier, Fabiana Fosca Ferrara, Ilaria Chiarucci, Paolo Carminati, Mineko Terao, and Claudio Pisano From the Laboratory of Molecular Biology, Centro Catullo e Daniela Borgomainerio, Istituto di Ricerche Farmacologiche "Mario Negri", and Facoltà di Agraria, Università degli Studi di Milano, Milan, Italy; Facoltà di Chimica, Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy; and Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Pomezia, Italy. Retinoid-related molecules (RRMs) are derivatives of retinoic acid and promising antileukemic agents with a mechanism of action different from that of other common chemotherapeutics. Here, we describe a novel chemical series designed against the RRM prototype, CD437. This includes molecules with apoptotic effects in acute promyelocytic leukemia and other myelogenous leukemia cell lines, as well as ST2065, an RRM with antagonistic properties. The most interesting apoptotic agent is ST1926, a compound more powerful than CD437 in vitro and orally active in vivo on severe combined immunodeficiency (SCID) mice that received transplants of NB4 cells. ST1926 has the same mechanism of action of CD437, as indicated by the ability to trans-activate retinoic acid receptor , to induce the phosphorylation of p38 and JNK, and to down-regulate the expression of many genes negatively modulated by CD437. ST1926 causes an immediate increase in the cytosolic levels of calcium that are directly related to the apoptotic potential of the RRMs considered. The intracellular calcium elevation is predominantly the result of an inhibition of the mitochondrial calcium uptake. The phenomenon is blocked by the ST2065 antagonist, the intracellular calcium chelator BAPTA (1,2 bis (2-aminophenoxy) ethane-N, N, N',N'-tetraacetic acid tetrakis (acetoxymethyl ester), and by high concentrations of calcium blockers of the dihydropyridine type, compounds that suppress ST1926-induced apoptosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Farhana, M. I. Dawson, L. Xu, and J. A. Fontana SHP and Sin3A expression are essential for adamantyl-substituted retinoid-related molecule-mediated nuclear factor-{kappa}B activation, c-Fos/c-Jun expression, and cellular apoptosis Mol. Cancer Ther., June 1, 2009; 8(6): 1625 - 1635. [Abstract] [Full Text] [PDF] L. Farhana, M. I. Dawson, M. Leid, L. Wang, D. D. Moore, G. Liu, Z. Xia, and J. A. Fontana Adamantyl-Substituted Retinoid-Related Molecules Bind Small Heterodimer Partner and Modulate the Sin3A Repressor Cancer Res., January 1, 2007; 67(1): 318 - 325. [Abstract] [Full Text] [PDF] E. Parrella, M. Gianni, M. Fratelli, M. M. Barzago, I. Raska Jr, L. Diomede, M. Kurosaki, C. Pisano, P. Carminati, L. Merlini, et al. Antitumor Activity of the Retinoid-Related Molecules (E)-3-(4'-Hydroxy-3'-adamantylbiphenyl-4-yl)acrylic Acid (ST1926) and 6-[3-(1-Adamantyl)-4-hydroxyphenyl]-2-naphthalene Carboxylic Acid (CD437) in F9 Teratocarcinoma: Role of Retinoic Acid Receptor {gamma} and Retinoid-Independent Pathways Mol. Pharmacol., September 1, 2006; 70(3): 909 - 924. [Abstract] [Full Text] [PDF] W. Liu, M. Guo, Y.-B. Xu, D. Li, Z.-N. Zhou, Y.-L. Wu, Z. Chen, S. C. Kogan, and G.-Q. Chen Induction of tumor arrest and differentiation with prolonged survival by intermittent hypoxia in a mouse model of acute myeloid leukemia Blood, January 15, 2006; 107(2): 698 - 707. [Abstract] [Full Text] [PDF] E. Parrella, M. Gianni', V. Cecconi, E. Nigro, M. M. Barzago, A. Rambaldi, C. Rochette-Egly, M. Terao, and E. Garattini Phosphodiesterase IV Inhibition by Piclamilast Potentiates the Cytodifferentiating Action of Retinoids in Myeloid Leukemia Cells: CROSS-TALK BETWEEN THE cAMP AND THE RETINOIC ACID SIGNALING PATHWAYS J. Biol. Chem., October 1, 2004; 279(40): 42026 - 42040. [Abstract] [Full Text] [PDF]

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