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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2579-2588. Prepublished online as a Blood First Edition Paper on November 7, 2006; DOI 10.1182/blood-2006-07-027326. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-07-027326v1 109/6/2579    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 Isham, C. R. Articles by Bible, K. C. Search for Related Content PubMed PubMed Citation Articles by Isham, C. R. Articles by Bible, K. C. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Chaetocin: a promising new antimyeloma agent with in vitro and in vivo activity mediated via imposition of oxidative stress Crescent R. Isham1, Jennifer D. Tibodeau1, Wendy Jin1, Ruifang Xu1, Michael M. Timm2, and Keith C. Bible1 1 Division of Medical Oncology, Department of Oncology; 2 Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN Chaetocin, a thiodioxopiperazine natural product previously unreported to have anticancer effects, was found to have potent antimyeloma activity in IL-6–dependent and –independent myeloma cell lines in freshly collected sorted and unsorted patient CD138+ myeloma cells and in vivo. Chaetocin largely spares matched normal CD138– patient bone marrow leukocytes, normal B cells, and neoplastic B-CLL (chronic lymphocytic leukemia) cells, indicating a high degree of selectivity even in closely lineage-related B cells. Furthermore, chaetocin displays superior ex vivo antimyeloma activity and selectivity than doxorubicin and dexamethasone, and dexamethasone- or doxorubicin-resistant myeloma cell lines are largely non–cross-resistant to chaetocin. Mechanistically, chaetocin is dramatically accumulated in cancer cells via a process inhibited by glutathione and requiring intact/unreduced disulfides for uptake. Once inside the cell, its anticancer activity appears mediated primarily through the imposition of oxidative stress and consequent apoptosis induction. Moreover, the selective antimyeloma effects of chaetocin appear not to reflect differential intracellular accumulation of chaetocin but, instead, heightened sensitivity of myeloma cells to the cytotoxic effects of imposed oxidative stress. Considered collectively, chaetocin appears to represent a promising agent for further study as a potential antimyeloma therapeutic. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. M. Cook, S. T. Hilton, J. Mecinovic, W. B. Motherwell, W. D. Figg, and C. J. Schofield Epidithiodiketopiperazines Block the Interaction between Hypoxia-inducible Factor-1{alpha} (HIF-1{alpha}) and p300 by a Zinc Ejection Mechanism J. Biol. Chem., September 25, 2009; 284(39): 26831 - 26838. [Abstract] [Full Text] [PDF] L. Ellis, P. W. Atadja, and R. W. Johnstone Epigenetics in cancer: Targeting chromatin modifications Mol. Cancer Ther., June 1, 2009; 8(6): 1409 - 1420. [Abstract] [Full Text] [PDF]

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