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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 7, 2007 Accepted January 16, 2008 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 Moarbess, Hiba El-Hajj, Youmna Kfoury, Marwan E. El-Sabban, Yves Lepelletier, Olivier Hermine, Carine Deleuze-Masquefa, Pierre-Antoine Bonnet, and Ali Bazarbachi* EA 4215, Phrmacochimie et Biomolecules, Universite Montpellier I, Faculte de Pharmacie, Montpellier, France Department of Internal Medicine, American University of Beirut, Beirut, Lebanon Department of Human Morphology Faculty of Medicine, American University of Beirut, Beirut, Lebanon CNRS UMR 8603 and Department of Hematology, Necker Hospital, Paris, France * Corresponding author; email: bazarbac{at}aub.edu.lb. 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, EAPB0203, 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, while normal resting or activated T lymphocytes were resistant. EAPB0203 treatment significantly down-regulated the anti-apoptotic 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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