4.5 Article

15-Methylene-Eburnamonine Kills Leukemic Stem Cells and Reduces Engraftment in a Humanized Bone Marrow Xenograft Mouse Model of Leukemia

Journal

CHEMMEDCHEM
Volume 11, Issue 21, Pages 2392-2397

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201600334

Keywords

cancer stem cells; glutathione; leukemia; natural products; xenograft models

Funding

  1. US National Cancer Institute [1R21A141039]
  2. NIH/NCRR [RR025761]

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Recent studies suggest that leukemia stem cells (LSCs) play a critical role in the initiation, propagation, and relapse of leukemia. Herein we show that (-)-15-methylene-eburnamonine, a derivative of the alkaloid (-)-eburnamonine, is cytotoxic against acute and chronic lymphocytic leukemias (ALL and CLL) and acute myelogenous leukemia (AML). The agent also decreases primary LSC frequency invitro. The cytotoxic effects appear to be mediated via the oxidative stress pathways. Furthermore, we show that the compound kills AML, ALL, and CLL stem cells. By the use of a novel humanized bone marrow murine model of leukemia (huBM/NSG), it was found to decrease progenitor cell engraftment.

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