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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5455-5462. Prepublished online as a Blood First Edition Paper on February 22, 2007; DOI 10.1182/blood-2006-12-063958. This Article Full Text (PDF) All Versions of this Article: blood-2006-12-063958v1 109/12/5455    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 Wang, M. Articles by Yi, Q. Search for Related Content PubMed PubMed Citation Articles by Wang, M. Articles by Yi, Q. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 20, 2006 Accepted February 16, 2007 Atiprimod inhibits the growth of mantle cell lymphoma in vitro and in vivo and induces apoptosis via activating the mitochondrial pathways Michael Wang, Liang Zhang, Xiaohong Han, Jing Yang, Jianfei Qian, Sungyoul Hong, Felipe Samaniego, Jorge Romaguera, and Qing Yi* Dept of Lymphoma & Myeloma, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX * Corresponding author; email: qyi{at}mdanderson.org. Atiprimod is a novel cationic amphiphilic compound and has been shown to exert antimyeloma effects both in vitro and in mouse experiments. This study was undertaken to evaluate the therapeutic efficacy of atiprimod on mantle cell lymphoma (MCL) and elucidate the mechanism by which it induces cell apoptosis. Atiprimod inhibited the growth and induced apoptosis of MCL cell lines and freshly isolated primary tumor cells in vitro. More importantly, atiprimod significantly inhibited tumor growth in vivo and prolonged the survival of tumor-bearing mice. However, atiprimod also exhibited lower cytotoxicity towards normal lymphocytes. Atiprimod activated c-Jun N-terminal protein kinases (JNK) and upregulated the level of Bax, Bad, and phosphorylated Bcl-2, resulting in release of apoptosis-inducing factor (AIF) and cytochrome c from mitochondria and activation and cleavage of caspase-9, caspase-3, and PARP. However, AIF, but not activation of caspases or PARP, was responsible for apoptosis in MCL cells because an AIF inhibitor, but not pan-caspase or paspase-9 inhibitors, completely abrogated atiprimod-induced apoptosis. Taken together, our results demonstrate that atiprimod displays a strong anti-MCL activity. Cell apoptosis was induced mainly via activation of the AIF pathway. These results support the use of atiprimod as a potential agent in MCL chemotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Wang, L. Zhang, X. Han, J. Yang, J. Qian, S. Hong, P. Lin, Y. Shi, J. Romaguera, L. W. Kwak, et al. A Severe Combined Immunodeficient-hu In vivo Mouse Model of Human Primary Mantle Cell Lymphoma Clin. Cancer Res., April 1, 2008; 14(7): 2154 - 2160. [Abstract] [Full Text] [PDF]

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