15-Methylene-Eburnamonine Kills Leukemic Stem Cells and Reduces Engraftment in a Humanized Bone Marrow Xenograft Mouse Model of Leukemia.
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.
Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.
Dilini C
DC
Gunasekara
Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.
Mary M
MM
Zheng
Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.
Tara
T
Mojtahed
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA.
James R
JR
Woods
Department of Pharmaceutical Sciences, Albany College of Pharmacy, Colchester, VT, USA.
Tamer E
TE
Fandy
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA.
Mark V
MV
Riofski
Division of Neurosciences, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
Carlotta A
CA
Glackin
Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, USA.|Department of Pharmaceutics and Industrial Pharmacy, Helwan University, Cairo, Egypt.
Hazem E
HE
Hassan
zPredicta, Palo Alto, CA, USA.
Julia
J
Kirshner
Department of BioMolecular Sciences, University of Mississippi, University, MS, USA.
David A
http://orcid.org/0000-0002-5434-1690
DA
Colby
cancer stem cells; glutathione; leukemia; natural products; xenograft models
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