Prevention of pancreatic cancer in a hamster model by cAMP decrease

Smoking and alcoholism are risk factors for the development of pancreatitis-associated pancreatic ductal adenocarcinoma (PDAC). We have previously shown that these cancers overexpressed stress neurotransmitters and cyclic adenosine monophosphate (cAMP) while the inhibitory neurotransmitter γ-aminobu...

Full description

Saved in:
Bibliographic Details
Published in:Oncotarget 2016-07, Vol.7 (28), p.44430-44441
Main Authors: Banerjee, Jheelam, Papu John, Arokya M S, Al-Wadei, Mohammed H, Schuller, Hildegard M
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - prevention & control
Animals
Carcinoma, Pancreatic Ductal - genetics
Carcinoma, Pancreatic Ductal - metabolism
Carcinoma, Pancreatic Ductal - prevention & control
Cricetinae
Cyclic AMP - metabolism
Disease Models, Animal
Female
Male
Mesocricetus
Pregnancy
Research Paper
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Smoking and alcoholism are risk factors for the development of pancreatitis-associated pancreatic ductal adenocarcinoma (PDAC). We have previously shown that these cancers overexpressed stress neurotransmitters and cyclic adenosine monophosphate (cAMP) while the inhibitory neurotransmitter γ-aminobutyric acid (GABA) was suppressed. Using a hamster model, the current study has tested the hypothesis that cAMP decrease by GABA supplementation in the drinking water prevents the development of pancreatitis-associated PDAC. Our data reveal strong preventive effects of GABA supplementation on the development of PDAC and pancreatic intraductal neoplasia (PanIN). ELISA assays and immunohistochemistry revealed significant decreases in the levels of cAMP and interleukin 6 accompanied by reductions in the expression of several cancer stem cell markers and phosphorylated signaling proteins, which stimulate cell proliferation, and migration in pancreatic exocrine cells of GABA treated animals. We conclude that cAMP decrease by GABA supplementation inhibits multiple cancer stimulating pathways in cancer stem cells, differentiated cancer cells and the immune system, identifying this approach as promising novel tool for the prevention of PDAC in individuals with a history of smoking and alcoholism.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.9790