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Growth hormone releasing hormone induces the expression of nitric oxide synthase

Nektarios Barabutis1, Agnieszka Siejka, Andrew V Schally

  • 1Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education, Miami, FL 33125, USA.

Journal of Cellular and Molecular Medicine
|June 4, 2010
PubMed

Insights

Growth hormone releasing hormone (GHRH) and its receptors are found in lung cancer cells. GHRH antagonists may treat cancers by reducing oxidative stress and tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Growth hormone releasing hormone (GHRH) and its receptors are implicated in various human cancers.
  • GHRH antagonists have demonstrated anti-tumor effects in preclinical cancer models.
  • GHRH signaling may influence reactive oxygen species metabolism in cancer.

Purpose of the Study:

  • To investigate the expression and function of GHRH and its receptors in the A549 human lung cancer cell line.
  • To elucidate the signaling pathways mediating GHRH's mitogenic effects in lung cancer.
  • To evaluate the potential of GHRH antagonists in counteracting GHRH-induced effects in cancer cells.

Main Methods:

  • Demonstration of GHRH receptor and GHRH expression in A549 cells.
  • Assessment of GHRH's mitogenic effect and its dependence on the extracellular receptor kinase (ERK)1/2 pathway.
  • Evaluation of the impact of GHRH on inducible nitric oxide synthase (iNOS), pNFκBp50, and cyclooxygenase 2 (COX-2) expression.
  • Inhibition studies using GHRH antagonist MZ-5-156 and MAPK inhibitor PD 098059.

Main Results:

  • GHRH and its receptors are expressed in A549 human lung cancer cells.
  • GHRH-induced mitogenesis in these cells is mediated by the ERK1/2 pathway, suppressed by MZ-5-156 and PD 098059.
  • GHRH upregulates inducible nitric oxide synthase (iNOS), pNFκBp50, and cyclooxygenase 2 (COX-2).
  • The GHRH antagonist MZ-5-156 effectively counteracted GHRH's effects on iNOS, pNFκBp50, and COX-2.

Conclusions:

  • GHRH signaling promotes proliferation in A549 lung cancer cells via the ERK1/2 pathway.
  • GHRH enhances the expression of iNOS, pNFκBp50, and COX-2, contributing to cancer-related processes.
  • GHRH antagonists show promise for treating cancers associated with increased oxidative and nitrosative stress.

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