15-Methylene-Eburnamonine Kills Leukemic Stem Cells and Reduces Engraftment in a Humanized Bone Marrow Xenograft Mouse Model of Leukemia
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- 作者：Dr. Dilini C. Gunasekara ; Dr. Mary M. Zheng ; Tara Mojtahed ; Dr. James R. Woods ; Prof. Tamer E. Fandy ; Dr. Mark V. Riofski ; Prof. Carlotta A. Glackin ; Prof. Hazem E. Hassan ; Dr. Julia Kirshner and Prof. David A. Colby
- 刊名：ChemMedChem
- 出版年：2016
- 出版时间：November 7, 2016
- 年：2016
- 卷：11
- 期：21
- 页码：2392-2397
- 全文大小：1067K
- ISSN：1860-7187
文摘
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 in vitro. 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.