PMID- 27542251
OWN - NLM
STAT- MEDLINE
DCOM- 20180222
LR  - 20220408
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 40
DP  - 2016 Oct 4
TI  - Antineoplastic effects and mechanisms of micheliolide in acute myelogenous 
      leukemia stem cells.
PG  - 65012-65023
LID - 10.18632/oncotarget.11342 [doi]
AB  - Leukemic stem cells (LSCs) greatly contribute to the initiation, relapse, and 
      multidrug resistance of leukemia. Current therapies targeting the cell cycle and 
      rapidly growing leukemic cells, including conventional chemotherapy, have little 
      effect due to the self-renewal and differentiated malignant cells replenishment 
      ability of LSCs despite their scarce supply in the bone marrow. Micheliolide 
      (MCL) is a natural guaianolide sesquiterpene lactone (GSL) which was discovered 
      in michelia compressa and michelia champaca plants, and has been shown to exert 
      selective cytotoxic effects on CD34+CD38- LSCs. In this study, we demonstrate 
      that DMAMCL significantly prolongs the lifespan of a mouse model of human acute 
      myelogenous leukemia (AML). Mechanistic investigations further revealed that MCL 
      exerted its cytotoxic effects via inhibition of NF-kappaB expression and activity, 
      and by generating intracellular reactive oxygen species (ROS). These results 
      provide valuable insight into the mechanisms underlying MCL-induced cytotoxicity 
      of LSCs, and support further preclinical investigations of MCL-related therapies 
      for the treatment of AML.
FAU - Ji, Qing
AU  - Ji Q
AD  - 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, P. R. China.
FAU - Ding, Ya-Hui
AU  - Ding YH
AD  - 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, P. R. China.
AD  - The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, 
      Nankai University, Tianjin 300071, P. R. China.
FAU - Sun, Yue
AU  - Sun Y
AD  - 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, P. R. China.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - 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, P. R. China.
FAU - Gao, Hui-Er
AU  - Gao HE
AD  - 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, P. R. China.
FAU - Song, He-Nan
AU  - Song HN
AD  - 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, P. R. China.
FAU - Yang, Ming
AU  - Yang M
AD  - 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, P. R. China.
FAU - Liu, Xiao-Lei
AU  - Liu XL
AD  - 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, P. R. China.
FAU - Zhang, Zi-Xiang
AU  - Zhang ZX
AD  - Department of Stomatology, Institute of Hematology and Blood Diseases Hospital, 
      Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 
      300020, P. R. China.
FAU - Li, Ying-Hui
AU  - Li YH
AD  - 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, P. R. China.
FAU - Gao, Ying-Dai
AU  - Gao YD
AD  - 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, P. R. China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Antineoplastic Agents)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sesquiterpenes, Guaiane)
RN  - 0 (micheliolide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis
MH  - Cell Self Renewal/drug effects
MH  - Disease Models, Animal
MH  - Humans
MH  - Leukemia, Myeloid, Acute/*drug therapy
MH  - Magnoliaceae/immunology
MH  - Mice
MH  - Mice, SCID
MH  - NF-kappa B/metabolism
MH  - Neoplastic Stem Cells/drug effects/*physiology
MH  - Reactive Oxygen Species/metabolism
MH  - Sesquiterpenes, Guaiane/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
PMC - PMC5323134
OTO - NOTNLM
OT  - leukemic stem cells
OT  - micheliolide
COIS- CONFLICTS OF INTEREST The authors declare no competing financial interests.
EDAT- 2016/08/20 06:00
MHDA- 2018/02/23 06:00
PMCR- 2016/10/04
CRDT- 2016/08/20 06:00
PHST- 2016/02/24 00:00 [received]
PHST- 2016/08/09 00:00 [accepted]
PHST- 2016/08/20 06:00 [pubmed]
PHST- 2018/02/23 06:00 [medline]
PHST- 2016/08/20 06:00 [entrez]
PHST- 2016/10/04 00:00 [pmc-release]
AID - 11342 [pii]
AID - 10.18632/oncotarget.11342 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Oct 4;7(40):65012-65023. doi: 10.18632/oncotarget.11342.