PMID- 22666346
OWN - NLM
STAT- MEDLINE
DCOM- 20121029
LR  - 20240317
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 5
DP  - 2012
TI  - Dihydroartemisinin enhances Apo2L/TRAIL-mediated apoptosis in pancreatic cancer 
      cells via ROS-mediated up-regulation of death receptor 5.
PG  - e37222
LID - 10.1371/journal.pone.0037222 [doi]
LID - e37222
AB  - BACKGROUND: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, 
      has recently shown antitumor activity in various cancer cells. Apo2 ligand or 
      tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is regarded 
      as a promising anticancer agent, but chemoresistance affects its efficacy as a 
      treatment strategy. Apoptosis induced by the combination of DHA and Apo2L/TRAIL 
      has not been well documented, and the mechanisms involved remain unclear. 
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that DHA enhances the efficacy of 
      Apo2L/TRAIL for the treatment of pancreatic cancer. We found that combined 
      therapy using DHA and Apo2L/TRAIL significantly enhanced apoptosis in BxPC-3 and 
      PANC-1 cells compared with single-agent treatment in vitro. The effect of DHA was 
      mediated through the generation of reactive oxygen species, the induction of 
      death receptor 5 (DR5) and the modulation of apoptosis-related proteins. However, 
      N-acetyl cysteine significantly reduced the enhanced apoptosis observed with the 
      combination of DHA and Apo2L/TRAIL. In addition, knockdown of DR5 by small 
      interfering RNA also significantly reduced the amount of apoptosis induced by DHA 
      and Apo2L/TRAIL. CONCLUSIONS/SIGNIFICANCE: These results suggest that DHA 
      enhances Apo2L/TRAIL-mediated apoptosis in human pancreatic cancer cells through 
      reactive oxygen species-mediated up-regulation of DR5.
FAU - Kong, Rui
AU  - Kong R
AD  - Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of 
      Harbin Medical University, Harbin, People's Republic of China.
FAU - Jia, Guang
AU  - Jia G
FAU - Cheng, Zhuo-xin
AU  - Cheng ZX
FAU - Wang, Yong-wei
AU  - Wang YW
FAU - Mu, Ming
AU  - Mu M
FAU - Wang, Shuang-jia
AU  - Wang SJ
FAU - Pan, Shang-ha
AU  - Pan SH
FAU - Gao, Yue
AU  - Gao Y
FAU - Jiang, Hong-chi
AU  - Jiang HC
FAU - Dong, De-li
AU  - Dong DL
FAU - Sun, Bei
AU  - Sun B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120530
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Artemisinins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 6A9O50735X (artenimol)
SB  - IM
EIN - PLoS One. 2012;7(10). doi:10.1371/annotation/f7203563-87dc-4d11-a1b7-958f81cf743a
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/*drug effects
MH  - Artemisinins/*pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Pancreatic Neoplasms/*pathology
MH  - Reactive Oxygen Species/*metabolism
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/*metabolism
MH  - TNF-Related Apoptosis-Inducing Ligand/*metabolism
MH  - Up-Regulation/*drug effects
PMC - PMC3364248
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/06/06 06:00
MHDA- 2012/10/30 06:00
PMCR- 2012/05/30
CRDT- 2012/06/06 06:00
PHST- 2011/07/24 00:00 [received]
PHST- 2012/04/15 00:00 [accepted]
PHST- 2012/06/06 06:00 [entrez]
PHST- 2012/06/06 06:00 [pubmed]
PHST- 2012/10/30 06:00 [medline]
PHST- 2012/05/30 00:00 [pmc-release]
AID - PONE-D-11-15534 [pii]
AID - 10.1371/journal.pone.0037222 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(5):e37222. doi: 10.1371/journal.pone.0037222. Epub 2012 May 30.