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Blood, 15 January 2006, Vol. 107, No. 2, pp. 716-724. Prepublished online as a Blood First Edition Paper on September 20, 2005; DOI 10.1182/blood-2005-02-0735. This Article Full Text (PDF) All Versions of this Article: 2005-02-0735v1 107/2/716    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 Dewan, Z. Articles by Yamamoto, N. Search for Related Content PubMed PubMed Citation Articles by Dewan, Z. Articles by Yamamoto, N. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 23, 2005 Accepted September 1, 2005 Efficient intervention of growth and infiltration of primary adult T-cell leukemia cells by an HIV protease inhibitor, ritonavir Zahidunnabi Dewan, Jun-nosuke Uchihara, Kazuo Terashima, Mitsuo Honda, Tetsutaro Sata, Mamoru Ito, Nobutaka Fujii, Kimiharu Uozumi, Kunihiro Tsukasaki, Masao Tomonaga, Yoko Kubuki, Akihiko Okayama, Masakazu Toi, Naoki Mori, and Naoki Yamamoto* Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan Division of Molecular Virology and Oncology, Graduate School of Medicine, University of Ryukyus, Okinawa, Japan Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan Central Institute for Experimental Animals, Kanagawa, Japan Department of Bioorganic Medical Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan Department of Hematology, Molecular Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan Second Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan Department of Laboratory Medicine, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan Division of Clinical Trials and Research, Breast Cancer Research and Treatment Program, Tokyo Metropolitan Komagome Hospital, Tokyo Medical Center for Cancer and Infectious Disease, Tokyo, Japan * Corresponding author; email: yamamoto.mmb{at}tmd.ac.jp. Adult T-cell leukemia (ATL), an aggressive malignancy of CD4+ T-cells associated with human T-cell leukemia virus type I (HTLV-I) infection, carries a very poor prognosis due to the resistance of leukemic cells to any conventional regimen including chemotherapy. We examined the effect of ritonavir, an HIV protease inhibitor, on HTLV-I-infected T-cell lines and primary ATL cells and found that it induced apoptosis and inhibited transcriptional activation of NF-B in these cells. Furthermore, ritonavir inhibited expression of Bcl-xL, survivin, c-Myc, and cyclin D2, the targets of NF-B. In NOD/SCID/cnull (NOG) mice, ritonavir very efficiently prevented tumor growth and leukemic infiltration in various organs of NOG mice at the same dose used for treatment of AIDS patients. Our data indicate that ritonavir has potent anti-NF-B and anti-tumor effects and might be clinically applicable for treatment of ATL. These results would provide new concept and novel platform for new drug development of leukemia and solid cancer as well. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Ito, T. Ishida, A. Utsunomiya, F. Sato, F. Mori, H. Yano, A. Inagaki, S. Suzuki, H. Takino, M. Ri, et al. Defucosylated Anti-CCR4 Monoclonal Antibody Exerts Potent ADCC against Primary ATLL Cells Mediated by Autologous Human Immune Cells in NOD/Shi-scid, IL-2R{gamma}null Mice In Vivo J. Immunol., October 1, 2009; 183(7): 4782 - 4791. [Abstract] [Full Text] [PDF] C. A. Pise-Masison, M. Radonovich, K. Dohoney, J. C. Morris, D. O'Mahony, M.-J. Lee, J. Trepel, T. A. Waldmann, J. E. Janik, and J. N. Brady Gene expression profiling of ATL patients: compilation of disease-related genes and evidence for TCF4 involvement in BIRC5 gene expression and cell viability Blood, April 23, 2009; 113(17): 4016 - 4026. [Abstract] [Full Text] [PDF] M. Z. Dewan, N. Takamatsu, T. Hidaka, K. Hatakeyama, S. Nakahata, J.-i. Fujisawa, H. Katano, N. Yamamoto, and K. Morishita Critical Role for TSLC1 Expression in the Growth and Organ Infiltration of Adult T-Cell Leukemia Cells In Vivo J. Virol., December 1, 2008; 82(23): 11958 - 11963. [Abstract] [Full Text] [PDF] S. Rabaaoui, F. Zouhiri, A. Lancon, H. Leh, J. d'Angelo, and E. Wattel Inhibitors of Strand Transfer That Prevent Integration and Inhibit Human T-Cell Leukemia Virus Type 1 Early Replication Antimicrob. Agents Chemother., October 1, 2008; 52(10): 3532 - 3541. [Abstract] [Full Text] [PDF] M. Kraus, E. Malenke, J. Gogel, H. Muller, T. Ruckrich, H. Overkleeft, H. Ovaa, E. Koscielniak, J. T. Hartmann, and C. Driessen Ritonavir induces endoplasmic reticulum stress and sensitizes sarcoma cells toward bortezomib-induced apoptosis Mol. Cancer Ther., July 1, 2008; 7(7): 1940 - 1948. [Abstract] [Full Text] [PDF]

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