GHRH antagonist MZ-5-156 increases the expression of AMPK in A549 lung cancer cells

Agnieszka Siejka, Nektarios Barabutis, Andrew V. Schally

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

AMP-activated protein kinase (AMPK) regulates cellular proliferation, growth and metabolism. Targeted activation of AMPK is considered an important therapeutic strategy for cancer treatment. To evaluate the effect of growth hormonereleasing hormone (GHRH) and its antagonist MZ-5-156 on the phosphorylation of AMPK and other related regulatory intracellular proteins we employed human non-small cell lung cancer cell line A549, which expresses GHRH receptors. Treatment of A549 cells with GHRH antagonist decreased cell proliferation and activated AMPK as well as glycogen synthase kinase (GSK)3β. Furthermore, MZ-5-156 inhibited Akt, the mammalian target of rapamycin (mTOR ) and its downstream target eIF4E which controls protein synthesis and cell growth. GHRH(1-29)NH 2 counteracted all these effects. HeLa human endometrial cancer cells which do not express any GHRH receptors were used as a negative control and GHRH did not induce the AMPK activation in these cells. Our results demonstrate for the first time that GHRH antagonists can regulate the AMPK metabolic pathway, which is crucial for the growth of non-small cell lung cancer and other major cancers.

Original languageEnglish (US)
Pages (from-to)3714-3718
Number of pages5
JournalCell Cycle
Volume10
Issue number21
DOIs
StatePublished - Nov 1 2011

Keywords

  • AMPK
  • GHRH
  • GHRH antagonist
  • GHRH receptor
  • Growth factor
  • Lung cancer
  • mTOR

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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