Get access

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

Authors

  • Hussein A. N. Al-Wadei,

    Corresponding author
    1. Experimental Oncology Laboratory, Department of Pathobiology, University of Tennessee, Knoxville, TN, USA
    2. Sana'a University, Sana'a, Republic of Yemen
    • Experimental Oncology Laboratory, Department of Pathobiology, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA Fax: +1-865-974-5616
    Search for more papers by this author
  • Mohammad F. Ullah,

    1. Experimental Oncology Laboratory, Department of Pathobiology, University of Tennessee, Knoxville, TN, USA
    Search for more papers by this author
  • Mohammed Al-Wadei

    1. Experimental Oncology Laboratory, Department of Pathobiology, University of Tennessee, Knoxville, TN, USA
    Search for more papers by this author
    • Please note that the author list has been changed after the initial online publication.

Errata

This article is corrected by:

  1. Errata: Erratum Volume 56, Issue 2, 352, Article first published online: February 2012

Abstract

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.

Get access to the full text of this article

Ancillary