PMID- 22041656
OWN - NLM
STAT- MEDLINE
DCOM- 20120828
LR  - 20211203
IS  - 1551-4005 (Electronic)
IS  - 1551-4005 (Linking)
VI  - 10
IP  - 21
DP  - 2011 Nov 1
TI  - GHRH antagonist MZ-5-156 increases the expression of AMPK in A549 lung cancer 
      cells.
PG  - 3714-8
LID - 10.4161/cc.10.21.17904 [doi]
AB  - 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)3beta. 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.
FAU - Siejka, Agnieszka
AU  - Siejka A
AD  - Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for 
      Research and Education, Miami, FL, USA. agnieszka.siejka@umed.lodz.pl
FAU - Barabutis, Nektarios
AU  - Barabutis N
FAU - Schally, Andrew V
AU  - Schally AV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20111101
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (MZ 5-156)
RN  - 86168-78-7 (Sermorelin)
RN  - 9034-39-3 (Growth Hormone-Releasing Hormone)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*genetics/metabolism
MH  - Carcinoma, Non-Small-Cell Lung/genetics/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Eukaryotic Initiation Factor-4E/metabolism
MH  - Gene Expression/*drug effects
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Growth Hormone-Releasing Hormone/*antagonists & inhibitors
MH  - HeLa Cells
MH  - Humans
MH  - Ki-67 Antigen/metabolism
MH  - Lung Neoplasms/genetics/*metabolism/pathology
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors
MH  - Sermorelin/*analogs & derivatives/pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2011/11/02 06:00
MHDA- 2012/08/29 06:00
CRDT- 2011/11/02 06:00
PHST- 2011/11/02 06:00 [entrez]
PHST- 2011/11/02 06:00 [pubmed]
PHST- 2012/08/29 06:00 [medline]
AID - 17904 [pii]
AID - 10.4161/cc.10.21.17904 [doi]
PST - ppublish
SO  - Cell Cycle. 2011 Nov 1;10(21):3714-8. doi: 10.4161/cc.10.21.17904. Epub 2011 Nov 
      1.