Journal
CELL CYCLE
Volume 10, Issue 21, Pages 3714-3718Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.10.21.17904
Keywords
GHRH; GHRH antagonist; GHRH receptor; AMPK; mTOR; lung cancer; growth factor
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Funding
- Medical Research Service of the Veterans Affairs Department, University of Miami Miller School of Medicine, Departments of Pathology and Medicine, Division of Hematology/Oncology, the South Florida Veterans Affairs Foundation for Research and Education
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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 hormone-releasing 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)3 beta. 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)NH2 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.
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