Literature DB >> 27677525

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

Dilini C Gunasekara1, Mary M Zheng1, Tara Mojtahed1, James R Woods2, Tamer E Fandy3, Mark V Riofski2, Carlotta A Glackin4, Hazem E Hassan5,6, Julia Kirshner7, David A Colby8.   

Abstract

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.
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Entities:  

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

Year:  2016        PMID： 27677525      PMCID： PMC5373928          DOI： 10.1002/cmdc.201600334

Source DB:  PubMed          Journal:  ChemMedChem        ISSN： 1860-7179            Impact factor:   3.466


  29 in total

Review 1.  Natural Products as Sources of New Drugs from 1981 to 2014.

Authors:  David J Newman; Gordon M Cragg
Journal:  J Nat Prod       Date:  2016-02-07       Impact factor: 4.050

2.  Synthesis of 15-methylene-eburnamonine from (+)-vincamine, evaluation of anticancer activity, and investigation of mechanism of action by quantitative NMR.

Authors:  James R Woods; Mark V Riofski; Mary M Zheng; Melissa A O'Banion; Huaping Mo; Julia Kirshner; David A Colby
Journal:  Bioorg Med Chem Lett       Date:  2013-09-06       Impact factor: 2.823

3.  The natural products parthenolide and andrographolide exhibit anti-cancer stem cell activity in multiple myeloma.

Authors:  Ellen J Gunn; John T Williams; Daniel T Huynh; Michael J Iannotti; Changho Han; Francis J Barrios; Stephen Kendall; Carlotta A Glackin; David A Colby; Julia Kirshner
Journal:  Leuk Lymphoma       Date:  2011-03-21

4.  A novel nonobese diabetic/severe combined immunodeficient xenograft model for chronic lymphocytic leukemia reflects important clinical characteristics of the disease.

Authors:  Jan Dürig; Peter Ebeling; Florian Grabellus; Ursula R Sorg; Michael Möllmann; Philipp Schütt; Joachim Göthert; Ludger Sellmann; Siegfried Seeber; Michael Flasshove; Ulrich Dührsen; Thomas Moritz
Journal:  Cancer Res       Date:  2007-09-15       Impact factor: 12.701

5.  Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region.

Authors:  Fumihiko Ishikawa; Shuro Yoshida; Yoriko Saito; Atsushi Hijikata; Hiroshi Kitamura; Satoshi Tanaka; Ryu Nakamura; Toru Tanaka; Hiroko Tomiyama; Noriyuki Saito; Mitsuhiro Fukata; Toshihiro Miyamoto; Bonnie Lyons; Koichi Ohshima; Naoyuki Uchida; Shuichi Taniguchi; Osamu Ohara; Koichi Akashi; Mine Harada; Leonard D Shultz
Journal:  Nat Biotechnol       Date:  2007-10-21       Impact factor: 54.908

6.  A cell initiating human acute myeloid leukaemia after transplantation into SCID mice.

Authors:  T Lapidot; C Sirard; J Vormoor; B Murdoch; T Hoang; J Caceres-Cortes; M Minden; B Paterson; M A Caligiuri; J E Dick
Journal:  Nature       Date:  1994-02-17       Impact factor: 49.962

Review 7.  The leukemic stem cell niche: current concepts and therapeutic opportunities.

Authors:  Steven W Lane; David T Scadden; D Gary Gilliland
Journal:  Blood       Date:  2009-04-28       Impact factor: 22.113

8.  Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells.

Authors:  Shanshan Pei; Mohammad Minhajuddin; Kevin P Callahan; Marlene Balys; John M Ashton; Sarah J Neering; Eleni D Lagadinou; Cheryl Corbett; Haobin Ye; Jane L Liesveld; Kristen M O'Dwyer; Zheng Li; Lei Shi; Patricia Greninger; Jeffrey Settleman; Cyril Benes; Fred K Hagen; Joshua Munger; Peter A Crooks; Michael W Becker; Craig T Jordan
Journal:  J Biol Chem       Date:  2013-10-02       Impact factor: 5.157

9.  In vitro characterization of transport and metabolism of the alkaloids: vincamine, vinpocetine and eburnamonine.

Authors:  Tamer E Fandy; Inas Abdallah; Maan Khayat; David A Colby; Hazem E Hassan
Journal:  Cancer Chemother Pharmacol       Date:  2015-12-14       Impact factor: 3.333

10.  BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors.

Authors:  Mhairi Copland; Francesca Pellicano; Linda Richmond; Elaine K Allan; Ashley Hamilton; Francis Y Lee; Roberto Weinmann; Tessa L Holyoake
Journal:  Blood       Date:  2007-12-21       Impact factor: 22.113
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  1 in total

1.  Mycobacterium tuberculosis virulence inhibitors discovered by Mycobacterium marinum high-throughput screening.

Authors:  Hasan Tükenmez; Isabel Edström; Ramesh Ummanni; Stina Berglund Fick; Charlotta Sundin; Mikael Elofsson; Christer Larsson
Journal:  Sci Rep       Date:  2019-01-10       Impact factor: 4.379
  1 in total

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