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Social stress promotes and γ-aminobutyric acid inhibits tumor growth in mouse models of non small cell lung cancer
Cancer Prevention Research (2011)
  • Hussein A.N. Al-Wadei, University of Tennessee - Knoxville
  • Howard K. Plummer III, University of Tennessee - Knoxville
  • Mohammad F. Ullah, University of Tennessee - Knoxville
  • Benjamin Unger, University of Tennessee - Knoxville
  • Joel Brody, University of Tennessee - Knoxville
  • Hildegard M. Schuller, University of Tennessee, Knoxville
Abstract

Psychological distress is associated with increased lung cancer incidence and mortality. We have shown that non small cell lung cancer (NSCLC) cells in vitro are stimulated by the cAMP-dependent activation of CREB and ERK downstream of beta-adrenergic receptors and that this pathway is inhibited by the neurotransmitter γ-aminobutyric acid (GABA). Because the stress neurotransmitters noradrenalin and adrenaline are beta-adrenergic agonists, the current study has tested the hypothesis that social stress stimulates NSCLC growth in vivo and that GABA inhibits this effect. Social stress was induced in mice carrying xenografts from two NSCLC cell lines in the presence and absence of treatment with GABA. Xenograft sizes were measured after 30 days. Noradrenalin, adrenalin, cortisol, GABA and cAMP were measured in blood and tumor tissues by immunoassays. Expression of nicotinic receptors in the xenografts was assessed by real-time PCR and Western blotting. Protein expression of p-CREB, CREB, p-ERK, ERK and glutamate decarboxylase (GAD) 65 and 67 were determined by Western blotting. Xenograft sizes in stress-exposed mice were significantly increased. Nicotinic acetylcholine receptor (nAChR) subunits α3, α4, α5, and α7 in xenograft tissues showed posttranscriptional induction. Noradrenalin, adrenalin and cortisol were elevated in serum and xenograft tissue while GABA was suppressed. Levels of cAMP, p-CREB and p-ERK were increased while GAD 65 and GAD 67 were suppressed in tumor tissue. Treatment with GABA reversed the effects of stress. Our findings suggest that social stress stimulates NSCLC by increasing nAChR-mediated stress neurotransmitter signaling and that GABA is a promising novel agent for NSCLC intervention. DOI: doi: 10.1158/1940-6207.CAPR-11-0177

Keywords
  • non small cell lung cancer,
  • NSCLC,
  • nicotinic receptors,
  • neurotransmitter γ-aminobutyric acid,
  • GABA
Publication Date
2011
Citation Information
Hussein A.N. Al-Wadei, Howard K. Plummer III, Mohammad F. Ullah, Benjamin Unger, et al.. "Social stress promotes and γ-aminobutyric acid inhibits tumor growth in mouse models of non small cell lung cancer" Cancer Prevention Research (2011)
Available at: http://works.bepress.com/hildegard_schuller/21/