PMID- 28473664
OWN - NLM
STAT- MEDLINE
DCOM- 20180418
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 24
DP  - 2017 Jun 13
TI  - Antineoplastic effects of CPPTL via the ROS/JNK pathway in acute myeloid 
      leukemia.
PG  - 38990-39000
LID - 10.18632/oncotarget.17166 [doi]
AB  - Drug resistance and human leukocyte antigen (HLA) matching limit conventional 
      treatment of acute myeloid leukemia (AML). Although several small molecule drugs 
      are clinically used, single drug administration is not sufficient to cure AML, 
      which has a high molecular diversity. Metabolic homeostasis plays a key role in 
      determining cellular fate. Appropriate levels of reactive oxygen species (ROS) 
      maintain the redox system balance, and excessive amounts of ROS cause oxidative 
      damage, thus providing a strategy to eliminate cancer cells. CPPTL is a novel 
      analogue of parthenolide that exhibited significant cytotoxicity to AML cells in 
      vitro and induced apoptosis in a dose-dependent manner. Additionally, CPPTL's 
      prodrug DMA-CPPTL decreased the burden of AML engraftment and prolonged survival 
      in a mouse model administered human primary AML cells in vivo. CPPTL induced 
      apoptosis of AML cells by stimulating ROS production, and accumulation of ROS 
      then activated the JNK pathway, thereby promoting mitochondrial damage. These 
      results demonstrated that CPPTL effectively eradicated AML cells in vitro and in 
      vivo and suggested that CPPTL may be a novel candidate for auxiliary AML therapy.
FAU - Gao, Hui-Er
AU  - Gao HE
AD  - State Key Laboratory of Experimental Hematology, Institute of Hematology and 
      Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Tianjin 300020, P. R. China.
FAU - Sun, Yue
AU  - Sun Y
AD  - State Key Laboratory of Experimental Hematology, Institute of Hematology and 
      Blood Diseases Hospital, 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 Medicinal Chemical Biology, College of Pharmacy, Nankai 
      University, Tianjin 300353, P. R. China.
FAU - Long, Jing
AU  - Long J
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai 
      University, Tianjin 300353, P. R. China.
FAU - Liu, Xiao-Lei
AU  - Liu XL
AD  - State Key Laboratory of Experimental Hematology, Institute of Hematology and 
      Blood Diseases Hospital, 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 
      Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Tianjin 300020, P. R. China.
FAU - Ji, Qing
AU  - Ji Q
AD  - State Key Laboratory of Experimental Hematology, 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 
      Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Tianjin 300020, P. R. China.
FAU - Chen, Yue
AU  - Chen Y
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai 
      University, Tianjin 300353, P. R. China.
FAU - Zhang, Quan
AU  - Zhang Q
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai 
      University, Tianjin 300353, P. R. China.
FAU - Gao, Ying-Dai
AU  - Gao YD
AD  - State Key Laboratory of Experimental Hematology, Institute of Hematology and 
      Blood Diseases Hospital, 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 (CPPTL compound)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sesquiterpenes)
RN  - 2RDB26I5ZB (parthenolide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Humans
MH  - *Leukemia, Myeloid, Acute
MH  - MAP Kinase Signaling System/*drug effects
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Reactive Oxygen Species/*metabolism
MH  - Sesquiterpenes/chemistry/*pharmacology
MH  - Xenograft Model Antitumor Assays
PMC - PMC5503589
OTO - NOTNLM
OT  - CPPTL
OT  - JNK pathway
OT  - ROS
OT  - acute myeloid leukemia
COIS- CONFLICTS OF INTEREST The authors declare that they have no competing interests.
EDAT- 2017/05/06 06:00
MHDA- 2018/04/19 06:00
PMCR- 2017/06/13
CRDT- 2017/05/06 06:00
PHST- 2017/02/23 00:00 [received]
PHST- 2017/04/03 00:00 [accepted]
PHST- 2017/05/06 06:00 [pubmed]
PHST- 2018/04/19 06:00 [medline]
PHST- 2017/05/06 06:00 [entrez]
PHST- 2017/06/13 00:00 [pmc-release]
AID - 17166 [pii]
AID - 10.18632/oncotarget.17166 [doi]
PST - ppublish
SO  - Oncotarget. 2017 Jun 13;8(24):38990-39000. doi: 10.18632/oncotarget.17166.