title: Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells.
abstract: BACKGROUND
  The poor outcomes for patients diagnosed with acute myeloid leukemia (AML) are largely attributed to leukemia stem cells (LSCs) which are difficult to eliminate with conventional therapy and responsible for relapse. Thus, new therapeutic strategies which could selectively target LSCs in clinical leukemia treatment and avoid drug resistance are urgently needed. However, only a few small molecules have been reported to show anti-LSCs activity.
  
  
  METHODS
  The aim of the present study was to identify alantolactone as novel agent that can ablate acute myeloid leukemia stem and progenitor cells from AML patient specimens and evaluate the anticancer activity of alantolactone in vitro and in vivo.
  
  
  RESULTS
  The present study is the first to demonstrate that alantolactone, a prominent eudesmane-type sesquiterpene lactone, could specifically ablate LSCs from AML patient specimens. Furthermore, in comparison to the conventional chemotherapy drug, cytosine arabinoside (Ara-C), alantolactone showed superior effects of leukemia cytotoxicity while sparing normal hematopoietic cells. Alantolactone induced apoptosis with a dose-dependent manner by suppression of NF-kB and its downstream target proteins. DMA-alantolactone, a water-soluble prodrug of alantolactone, could suppress tumor growth in vivo.
  
  
  CONCLUSIONS
  Based on these results, we propose that alantolactone may represent a novel LSCs-targeted therapy and eudesmane-type sesquiterpene lactones offer a new scaffold for drug discovery towards anti-LSCs agents.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China.
authors.forename: Huier
authors.initials: H
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Gordon Center for Medical Imaging, Massachusetts General Hospital, Boston, 02114, MA, USA.|Department of Radiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Vasdev
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, People's Republic of China.
authors.forename: Yingdai
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China. zhangquan612@163.com.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
keywords: Acute myeloid leukemia stem cells; Alantolactone; Apoptosis; KG1a