Please note that the author list has been changed after the initial online publication.
GABA (γ-aminobutyric acid), a non-protein amino acid counters the β-adrenergic cascade-activated oncogenic signaling in pancreatic cancer: A review of experimental evidence
Version of Record online: 1 AUG 2011
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 55, Issue 12, pages 1745–1758, December 2011
How to Cite
Al-Wadei, H. A. N., Ullah, M. F. and Al-Wadei, M. (2011), GABA (γ-aminobutyric acid), a non-protein amino acid counters the β-adrenergic cascade-activated oncogenic signaling in pancreatic cancer: A review of experimental evidence. Mol. Nutr. Food Res., 55: 1745–1758. doi: 10.1002/mnfr.201100229
- Issue online: 2 DEC 2011
- Version of Record online: 1 AUG 2011
- Manuscript Accepted: 27 MAY 2011
- Manuscript Revised: 26 MAY 2011
- Manuscript Received: 2 APR 2011
Vol. 56, Issue 2, 352, Version of Record online: 14 MAR 2012
- Cell signaling;
GABA is a bioactive constituent of fruits, vegetables, cereals and is believed to play a role in defense against stress in plants. In animals, it acts as an inhibitory neurotransmitter in brain while also expressed in non-neuronal cells. Studies have implicated the regulator of fight or flight stress responses, β-AR signaling cascade, as mediators of cancer growth and progression in in vitro and in vivo models of pancreatic malignancies. Pancreatic cancer is the fourth leading cause of cancer mortality in western countries. This malignancy is generally unresponsive to conventional radio- and chemotherapy, resulting in mortality rate near 100% within 6 months of diagnosis. We review a series of experiments from our laboratory and those of others examining the contribution of this signaling network to pancreatic and other human malignancies. Stimulation of the β-adrenergic receptor by lifestyle and environmental factors, as well as a pre-existing risk of neoplasm, activates downstream effector molecules that lead to pro-oncogenic signaling and thereby aid cancer growth. GABAergic signaling mediated by the serpentine receptor GABAB acts as an antagonist to β-adrenergic cascade by intercepting adenylyl cyclase. These evidences enhance the pharmacological value of human diets rich in GABA for use as an adjuvant to standard therapies.