PMID- 20299603
OWN - NLM
STAT- MEDLINE
DCOM- 20100617
LR  - 20220302
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 298
IP  - 6
DP  - 2010 Jun
TI  - Modulatory effect of curcumin on survival of irradiated human intestinal 
      microvascular endothelial cells: role of Akt/mTOR and NF-kappaB.
PG  - G865-77
LID - 10.1152/ajpgi.00339.2009 [doi]
AB  - Radiation therapy is an essential modality in the treatment of colorectal 
      cancers. Radiation exerts an antiangiogenic effect on tumors, inhibiting 
      endothelial proliferation and survival in the tumor microvasculature. However, 
      damage from low levels of irradiation can induce a paradoxical effect, 
      stimulating survival in endothelial cells. We used human intestinal microvascular 
      endothelial cells (HIMEC) to define effects of radiation on these gut-specific 
      endothelial cells. Low-level irradiation (1-5 Gy) activates NF-kappaB and the 
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which is involved in cell cycle 
      reentry and cell survival in HIMEC. A downstream target of PI3K/Akt is mammalian 
      target of rapamycin (mTOR), which contributes to endothelial proliferation and 
      angiogenesis. The aim of this study was to investigate the signaling molecules 
      involved in the radiosensitizing effects of curcumin on HIMEC subjected to low 
      levels of irradiation. We have demonstrated that exposure of HIMEC to low levels 
      of irradiation induced Akt and mTOR phosphorylation, which was attenuated by 
      curcumin, rapamycin, LY294002, and mTOR small interference RNA (siRNA). 
      Activation of NF-kappaB by low levels of irradiation was inhibited by curcumin, 
      SN-50, and mTOR siRNA. Curcumin also induced apoptosis by induction of caspase-3 
      cleavage in irradiated HIMEC. In conclusion, curcumin significantly inhibited 
      NF-kappaB and attenuated the effect of irradiation-induced prosurvival signaling 
      through the PI3K/Akt/mTOR and NF-kappaB pathways in these gut-specific 
      endothelial cells. Curcumin may be a potential radiosensitizing agent for 
      enhanced antiangiogenic effect in colorectal cancer radiation therapy.
FAU - Rafiee, Parvaneh
AU  - Rafiee P
AD  - Department. of Surgery, Medical College of Wisconsin, 8701 Watertown Plank Rd., 
      Milwaukee, WI 53226, USA. prafiee@mcw.edu
FAU - Binion, David G
AU  - Binion DG
FAU - Wellner, Michael
AU  - Wellner M
FAU - Behmaram, Behnaz
AU  - Behmaram B
FAU - Floer, Martin
AU  - Floer M
FAU - Mitton, Elizabeth
AU  - Mitton E
FAU - Nie, Linghui
AU  - Nie L
FAU - Zhang, Zhihong
AU  - Zhang Z
FAU - Otterson, Mary F
AU  - Otterson MF
LA  - eng
GR  - U19 AI067734/AI/NIAID NIH HHS/United States
GR  - 5U19-AI067734/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100318
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (FOXO1 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Radiation-Sensitizing Agents)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Abnormalities, Radiation-Induced/drug therapy
MH  - Animals
MH  - Caspase 3/genetics/metabolism
MH  - Cell Death/drug effects/radiation effects
MH  - Cell Survival/drug effects/radiation effects
MH  - Curcumin/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/*drug effects/radiation effects
MH  - Forkhead Box Protein O1
MH  - Forkhead Transcription Factors/genetics/metabolism
MH  - Gene Expression Regulation
MH  - Gene Silencing
MH  - Humans
MH  - Intestines/blood supply/drug effects/radiation effects
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Male
MH  - Microvessels/cytology
MH  - NF-kappa B/genetics/*metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-mdm2/genetics/metabolism
MH  - RNA, Small Interfering
MH  - Radiation-Sensitizing Agents/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - TOR Serine-Threonine Kinases
PMC - PMC3774333
EDAT- 2010/03/20 06:00
MHDA- 2010/06/18 06:00
PMCR- 2011/06/01
CRDT- 2010/03/20 06:00
PHST- 2010/03/20 06:00 [entrez]
PHST- 2010/03/20 06:00 [pubmed]
PHST- 2010/06/18 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - ajpgi.00339.2009 [pii]
AID - GI-00339-2009 [pii]
AID - 10.1152/ajpgi.00339.2009 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2010 Jun;298(6):G865-77. doi: 
      10.1152/ajpgi.00339.2009. Epub 2010 Mar 18.