PMID- 24462866
OWN - NLM
STAT- MEDLINE
DCOM- 20140506
LR  - 20220316
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 444
IP  - 3
DP  - 2014 Feb 14
TI  - Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR 
      inhibition in cisplatin-resistant ovarian cancer cells: involvement of apoptosis 
      and autophagy.
PG  - 376-81
LID - S0006-291X(14)00077-1 [pii]
LID - 10.1016/j.bbrc.2014.01.053 [doi]
AB  - Dihydroartemisinin (DHA) exhibits anticancer activity in tumor cells but its 
      mechanism of action is unclear. Cisplatin (DDP) is currently the best known 
      chemotherapeutic available for ovarian cancer. However, tumors return de novo 
      with acquired resistance over time. Mammalian target of rapamycin (mTOR) is an 
      important kinase that regulates cell apoptosis and autophagy, and its 
      dysregulation has been observed in chemoresistant human cancers. Here, we show 
      that compared with control ovarian cancer cells (SKOV3), mTOR phosphorylation was 
      abnormally activated in cisplatin-resistant ovarian cancer cells (SKOV3/DDP) 
      following cisplatin monotherapy. Treatment with cisplatin combined with DHA could 
      enhance cisplatin-induced proliferation inhibition in SKOV3/DDP cells. This 
      mechanism is at least partially due to DHA deactivation of mTOR kinase and 
      promotion of apoptosis. Although autophagy was also induced by DHA, the reduced 
      cell death was not found by suppressing autophagic flux by Bafilomycin A1 (BAF). 
      Taken together, we conclude that inhibition of cisplatin-induced mTOR activation 
      is one of the main mechanisms by which DHA dramatically promotes its anticancer 
      effect in cisplatin-resistant ovarian cancer cells.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Feng, Xue
AU  - Feng X
AD  - Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin 
      Medical University, Harbin 150001, China.
FAU - Li, Ling
AU  - Li L
AD  - Department of Brain Cognition Computing Lab, University of Kent, Kent CT2 7NZ, 
      UK.
FAU - Jiang, Hong
AU  - Jiang H
AD  - Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin 
      Medical University, Harbin 150001, China.
FAU - Jiang, Keping
AU  - Jiang K
AD  - Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin 
      Medical University, Harbin 150001, China.
FAU - Jin, Ye
AU  - Jin Y
AD  - Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin 
      Medical University, Harbin 150001, China.
FAU - Zheng, Jianhua
AU  - Zheng J
AD  - Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin 
      Medical University, Harbin 150001, China. Electronic address: 
      zhengjianhua1115@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140122
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Artemisinins)
RN  - 6A9O50735X (artenimol)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Artemisinins/*pharmacology
MH  - Autophagy/*drug effects
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Cisplatin/*pharmacology
MH  - Female
MH  - Humans
MH  - Ovarian Neoplasms/*drug therapy/pathology
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Cisplatin
OT  - Dihydroartemisinin
OT  - Ovarian cancer
OT  - mTOR
EDAT- 2014/01/28 06:00
MHDA- 2014/05/07 06:00
CRDT- 2014/01/28 06:00
PHST- 2014/01/10 00:00 [received]
PHST- 2014/01/15 00:00 [accepted]
PHST- 2014/01/28 06:00 [entrez]
PHST- 2014/01/28 06:00 [pubmed]
PHST- 2014/05/07 06:00 [medline]
AID - S0006-291X(14)00077-1 [pii]
AID - 10.1016/j.bbrc.2014.01.053 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2014 Feb 14;444(3):376-81. doi: 
      10.1016/j.bbrc.2014.01.053. Epub 2014 Jan 22.