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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3770-3777. Prepublished online as a Blood First Edition Paper on January 24, 2008; DOI 10.1182/blood-2007-11-121913. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-11-121913v1 111/7/3770    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 Moarbess, G. Articles by Bazarbachi, A. Search for Related Content PubMed PubMed Citation Articles by Moarbess, G. Articles by Bazarbachi, A. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA EAPB0203, a member of the imidazoquinoxaline family, inhibits growth and induces caspase-dependent apoptosis in T-cell lymphomas and HTLV-I–associated adult T-cell leukemia/lymphoma Georges Moarbess1,2, Hiba El-Hajj2, Youmna Kfoury2, Marwan E. El-Sabban3, Yves Lepelletier4, Olivier Hermine4, Carine Deleuze-Masquéfa1, Pierre-Antoine Bonnet1, and Ali Bazarbachi2 1 Pharmacochimie et Biomolécules, Université Montpellier I, Faculté de Pharmacie, Montpellier, France; Departments of2 Internal Medicine and 3 Human Morphology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; and 4 Centre National de la Recherche Scientifique Unité Mixte de Recherche 8603 and Department of Hematology, Necker Hospital, Paris, France Imiquimod is an immune response modifier currently used as a topical treatment of genital warts, basal cell carcinoma, cutaneous metastasis of malignant melanoma, and vascular tumors. We developed more efficient killers from the same family of compounds that can induce apoptosis without the prominent pro-inflammatory response associated with imiquimod. Among these new products, tk;4EAPB0203, a member of the imidazo[1,2-a]quinoxalines, exhibits an important cytotoxic activity in vitro. HTLV-I–associated adult T-cell leukemia (ATL) and HTLV-I–negative peripheral T-cell lymphomas are associated with poor prognosis. Using potentially achievable concentrations of EAPB0203, we demonstrate inhibition of cell proliferation, G2/M cell- cycle arrest, and induction of apoptosis in HTLV-I–transformed and HTLV-I–negative malignant T cells and fresh ATL cells, whereas normal resting or activated T lymphocytes were resistant. EAPB0203 treatment significantly down-regulated the antiapoptotic proteins c-IAP-1 and Bcl-XL and resulted in a significant loss of mitochondrial membrane potential, cytoplasmic release of cytochrome c, and caspase-dependent apoptosis. Moreover, in HTLV-I–transformed cells only, EAPB0203 treatment stabilized p21 and p53 proteins but had no effect on NF-B activation. These results support a potential therapeutic role for EAPB0203 in ATL and HTLV-I–negative T-cell lymphomas, either as a systemic or topical therapy for skin lesions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. L. J. M. Smits, P. Ponsaerts, Z. N. Berneman, and V. F. I. Van Tendeloo The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy Oncologist, August 1, 2008; 13(8): 859 - 875. [Abstract] [Full Text] [PDF]

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