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A vasoactive intestinal peptide antagonist inhibits the growth of glioblastoma cells

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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.

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Authors and Affiliations

  1. National Cancer Institute, Medicine Branch, 20850, Rockville, MD

    Anita Sharma, James Walters & Terry W. Moody

  2. Israel Institute for Biological Research, Ness, 74100, Ziona, Israel

    Yehoshua Gozes

  3. Department of Organic Chemistry, Weizmann Institute of Science, 76100, Rehovot, Israel

    Mati Fridkin

  4. Section on Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, National Institute for Child Health and Human Development, 20892, Bethesda, MD

    Douglas Brennman

  5. Department of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv Univ., 69978, Tel Aviv, Israel

    Illana Gozes

Authors
  1. Anita Sharma
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  2. James Walters
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  3. Yehoshua Gozes
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  4. Mati Fridkin
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  5. Douglas Brennman
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  6. Illana Gozes
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  7. Terry W. Moody
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Correspondence to Terry W. Moody.

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Sharma, A., Walters, J., Gozes, Y. et al. A vasoactive intestinal peptide antagonist inhibits the growth of glioblastoma cells. J Mol Neurosci 17, 331–339 (2001). https://doi.org/10.1385/JMN:17:3:331

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  • DOI: https://doi.org/10.1385/JMN:17:3:331

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