PMID- 26929026
OWN - NLM
STAT- MEDLINE
DCOM- 20170323
LR  - 20201209
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Linking)
VI  - 30
IP  - 6
DP  - 2016 Jun
TI  - Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF 
      Signaling in Caco-2 Human Colon Carcinoma Cell Line Through a Selective 
      PPAR-alpha-Dependent Inhibition of Akt/mTOR Pathway.
PG  - 963-70
LID - 10.1002/ptr.5601 [doi]
AB  - Palmitoylethanolamide (PEA) is a nutraceutical compound that has been 
      demonstrated to improve intestinal inflammation. We aimed at evaluating its 
      antiproliferative and antiangiogenic effects in human colon adenocarcinoma Caco-2 
      cell line. Caco-2 cells were treated with increasing concentrations of PEA 
      (0.001, 0.01 and 0.1 muM) in the presence of peroxisome proliferator-activated 
      receptor-a (PPAR-alpha) or PPAR-gamma antagonists. Cell proliferation was evaluated by 
      performing a MTT assay. Vascular endothelial growth factor (VEGF) release was 
      estimated by ELISA, while the expression of VEGF receptor and the activation of 
      the Akt/mammalian target of rapamycin (mTOR) pathway were evaluated by western 
      blot analysis. PEA caused a significant and concentration-dependent decrease of 
      Caco-2 cell proliferation at 48 h. PEA administration significantly reduced in a 
      concentration-dependent manner VEGF secretion and VEGF receptor expression. 
      Inhibition of Akt phosphorylation and a downstream decrease of phospho-mTOR and 
      of p-p70S6K were observed as compared with untreated cells. PPAR-alpha, but not 
      PPAR-gamma antagonist, reverted all effects of PEA. PEA is able to decrease cell 
      proliferation and angiogenesis. The antiangiogenic effect of PEA depends on the 
      specific inhibition of the AkT/mTOR axis, through the activation of PPAR-alpha 
      pathway. If supported by in vivo models, our data pave the way to PEA 
      co-administration to the current chemotherapeutic regimens for colon carcinoma. 
      Copyright (c) 2016 John Wiley & Sons, Ltd.
CI  - Copyright (c) 2016 John Wiley & Sons, Ltd.
FAU - Sarnelli, Giovanni
AU  - Sarnelli G
AD  - Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, 
      Naples, Italy.
FAU - Gigli, Stefano
AU  - Gigli S
AD  - Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza 
      University of Rome, Rome, Italy.
FAU - Capoccia, Elena
AU  - Capoccia E
AD  - Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza 
      University of Rome, Rome, Italy.
FAU - Iuvone, Teresa
AU  - Iuvone T
AD  - Department of Pharmacy, University of Naples Federico II, Naples, Italy.
FAU - Cirillo, Carla
AU  - Cirillo C
AD  - Laboratory for Enteric NeuroScience (LENS), Translational Research Center for 
      Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
FAU - Seguella, Luisa
AU  - Seguella L
AD  - Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza 
      University of Rome, Rome, Italy.
FAU - Nobile, Nicola
AU  - Nobile N
AD  - Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza 
      University of Rome, Rome, Italy.
FAU - D'Alessandro, Alessandra
AU  - D'Alessandro A
AD  - Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, 
      Naples, Italy.
FAU - Pesce, Marcella
AU  - Pesce M
AD  - Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, 
      Naples, Italy.
FAU - Steardo, Luca
AU  - Steardo L
AD  - Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza 
      University of Rome, Rome, Italy.
FAU - Cuomo, Rosario
AU  - Cuomo R
AD  - Department of Clinical Medicine and Surgery, 'Federico II' University of Naples, 
      Naples, Italy.
FAU - Esposito, Giuseppe
AU  - Esposito G
AD  - Department of Physiology and Pharmacology 'Vittorio Erspamer', La Sapienza 
      University of Rome, Rome, Italy.
LA  - eng
PT  - Journal Article
DEP - 20160301
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - 0 (Amides)
RN  - 0 (Ethanolamines)
RN  - 0 (PPAR alpha)
RN  - 0 (Palmitic Acids)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 6R8T1UDM3V (palmidrol)
SB  - IM
MH  - Amides
MH  - Animals
MH  - Caco-2 Cells
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Colonic Neoplasms/*drug therapy
MH  - Down-Regulation/drug effects
MH  - Ethanolamines/*chemistry/therapeutic use
MH  - Humans
MH  - Neovascularization, Pathologic
MH  - PPAR alpha/*metabolism
MH  - Palmitic Acids/*chemistry/therapeutic use
MH  - Signal Transduction
MH  - Vascular Endothelial Growth Factor A/*metabolism
OTO - NOTNLM
OT  - Caco-2 human adenocarcinoma cell line
OT  - Palmitoylethanolamide (PEA)
OT  - angiogenesis
OT  - proliferation
EDAT- 2016/03/02 06:00
MHDA- 2017/03/24 06:00
CRDT- 2016/03/02 06:00
PHST- 2015/12/02 00:00 [received]
PHST- 2016/02/04 00:00 [revised]
PHST- 2016/02/05 00:00 [accepted]
PHST- 2016/03/02 06:00 [entrez]
PHST- 2016/03/02 06:00 [pubmed]
PHST- 2017/03/24 06:00 [medline]
AID - 10.1002/ptr.5601 [doi]
PST - ppublish
SO  - Phytother Res. 2016 Jun;30(6):963-70. doi: 10.1002/ptr.5601. Epub 2016 Mar 1.