Journal of Molecular Neuroscience

, Volume 17, Issue 3, pp 331–339 | Cite as

A vasoactive intestinal peptide antagonist inhibits the growth of glioblastoma cells

  • Anita Sharma
  • James Walters
  • Yehoshua Gozes
  • Mati Fridkin
  • Douglas Brennman
  • Illana Gozes
  • Terry W. Moody
Article

Abstract

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 transcriptasepolymerase chain reaction (RT-PCR), a major 305bp 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 µM VIPhyb significantly inhibited proliferation of U87, U118, and U373 cells. In vivo, 0.4 µg/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.

Index Entries

PACAP receptors glioblastoma VIP antagonist proliferation 

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Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  • Anita Sharma
    • 1
  • James Walters
    • 1
  • Yehoshua Gozes
    • 2
  • Mati Fridkin
    • 3
  • Douglas Brennman
    • 4
  • Illana Gozes
    • 5
  • Terry W. Moody
    • 1
  1. 1.National Cancer Institute, Medicine BranchRockville
  2. 2.Israel Institute for Biological Research, NessZionaIsrael
  3. 3.Department of Organic ChemistryWeizmann Institute of ScienceRehovotIsrael
  4. 4.Section on Developmental and Molecular Pharmacology, Laboratory of Developmental NeurobiologyNational Institute for Child Health and Human DevelopmentBethesda
  5. 5.Department of Clinical Biochemistry, Sackler School of MedicineTel Aviv Univ.Tel AvivIsrael

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