Document Detail

A vasoactive intestinal peptide antagonist inhibits the growth of glioblastoma cells.
MedLine Citation:
PMID:  11859929     Owner:  NLM     Status:  MEDLINE    
The effects of a vasoactive intestinal peptide (VIP) receptor antagonist (VIPhyb) on human glioblastoma cells were characterized. Pituitary adenylate cyclase activating polypeptide (125I-PACAP-27) bound with high affinity to U87, U118, and U373 cells. Specific 125I-PACAP-27 binding to U87 cells was inhibited, with high affinity, by PACAP but not VIP or VIPhyb (IC50 = 10, 1500, and 500 nM, respectively). By reverse transcriptase-polymerase chain reaction (RT-PCR), a major 305 bp band was observed indicative of PAC1 receptors. PACAP-27 caused cAMP elevation and the increase in cAMP caused by PACAP-27, was inhibited by the VIPhyb. Also, PACAP-27 caused cytosolic Ca2+ elevation in Fura-2AM loaded U87 cells and the VIPhyb inhibited this increase. Using the MTT growth assay, the VIPhyb was shown to inhibit glioblastoma growth in a concentration-dependent manner. Using a clonogenic assay in vitro, 10 microM VIPhyb significantly inhibited proliferation of U87, U118, and U373 cells. In vivo, 0.4 microg/kg VIPhyb inhibited U87 xenograft proliferation in nude mice. These results suggest that the VIPhyb antagonizes PAC1 receptors on glioblastoma cells and inhibits their proliferation.
A Sharma; J Walters; Y Gozes; M Fridkin; D Brenneman; I Gozes; T W Moody
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of molecular neuroscience : MN     Volume:  17     ISSN:  0895-8696     ISO Abbreviation:  J. Mol. Neurosci.     Publication Date:  2001 Dec 
Date Detail:
Created Date:  2002-02-25     Completed Date:  2002-08-21     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  9002991     Medline TA:  J Mol Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  331-9     Citation Subset:  IM    
National Cancer Institute, Medicine Branch, Rockville, MD 20850, USA.
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MeSH Terms
Calcium / metabolism
Cyclic AMP / metabolism
Cytosol / metabolism
Dose-Response Relationship, Drug
Glioblastoma / metabolism*
Mice, Nude
Neuropeptides / antagonists & inhibitors*,  metabolism
Neurotensin / metabolism,  pharmacology*
Pituitary Adenylate Cyclase-Activating Polypeptide
Receptors, Vasoactive Intestinal Peptide / antagonists & inhibitors,  drug effects*,  metabolism
Recombinant Fusion Proteins / metabolism,  pharmacology*
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Transplantation, Heterologous
Tumor Cells, Cultured / drug effects
Vasoactive Intestinal Peptide / metabolism,  pharmacology*
Reg. No./Substance:
0/ADCYAP1 protein, human; 0/Adcyap1 protein, mouse; 0/Neuropeptides; 0/Pituitary Adenylate Cyclase-Activating Polypeptide; 0/Receptors, Vasoactive Intestinal Peptide; 0/Recombinant Fusion Proteins; 125093-93-8/(VIP-neurotensin) hybrid antagonist; 37221-79-7/Vasoactive Intestinal Peptide; 39379-15-2/Neurotensin; 60-92-4/Cyclic AMP; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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