A Vasoactive Intestinal Peptide Antagonist Inhibits the Growth of Glioblastoma Cells

Overview

Journal J Mol Neurosci

Specialties Molecular Biology
Neurology

Date 2002 Feb 28

PMID 11859929

Citations 14

Authors

A Sharma

J Walters

Y Gozes

M Fridkin

D Brenneman

I Gozes

T W Moody

Affiliations

Soon will be listed here.

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 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.

Citing Articles

Glioma and Peptidergic Systems: Oncogenic and Anticancer Peptides.

Sanchez M, Mangas A, Covenas R Int J Mol Sci. 2024; 25(14).

PMID: 39063232 PMC: 11277022. DOI: 10.3390/ijms25147990.

Whole genome sequencing identifies genetic variants associated with neurogenic inflammation in rosacea.

Deng Z, Chen M, Zhao Z, Xiao W, Liu T, Peng Q Nat Commun. 2023; 14(1):3958.

PMID: 37402769 PMC: 10319783. DOI: 10.1038/s41467-023-39761-2.

Targeting vasoactive intestinal peptide-mediated signaling enhances response to immune checkpoint therapy in pancreatic ductal adenocarcinoma.

Ravindranathan S, Passang T, Li J, Wang S, Dhamsania R, Ware M Nat Commun. 2022; 13(1):6418.

PMID: 36302761 PMC: 9613684. DOI: 10.1038/s41467-022-34242-4.

Effect of PACAP on Hypoxia-Induced Angiogenesis and Epithelial-Mesenchymal Transition in Glioblastoma.

Maugeri G, DAmico A, Saccone S, Federico C, Rasa D, Caltabiano R Biomedicines. 2021; 9(8).

PMID: 34440169 PMC: 8392618. DOI: 10.3390/biomedicines9080965.

Multimodal Role of PACAP in Glioblastoma.

DAmico A, Maugeri G, Vanella L, Pittala V, Reglodi D, DAgata V Brain Sci. 2021; 11(8).

PMID: 34439613 PMC: 8391398. DOI: 10.3390/brainsci11080994.

References

Brenneman D, Gozes I . A femtomolar-acting neuroprotective peptide. J Clin Invest. 1996; 97(10):2299-307. PMC: 507310. DOI: 10.1172/JCI118672. View

Magistretti P, Morrison J . Noradrenaline- and vasoactive intestinal peptide-containing neuronal systems in neocortex: functional convergence with contrasting morphology. Neuroscience. 1988; 24(2):367-78. DOI: 10.1016/0306-4522(88)90338-7. View

Lilling G, Wollman Y, GOLDSTEIN M, Rubinraut S, Fridkin M, Brenneman D . Inhibition of human neuroblastoma growth by a specific VIP antagonist. J Mol Neurosci. 1994; 5(4):231-9. DOI: 10.1007/BF02736724. View

Magistretti P, Cardinaux J, Martin J . VIP and PACAP in the CNS: regulators of glial energy metabolism and modulators of glutamatergic signaling. Ann N Y Acad Sci. 1999; 865:213-25. DOI: 10.1111/j.1749-6632.1998.tb11181.x. View

Pandol S, Dharmsathaphorn K, Schoeffield M, Vale W, Rivier J . Vasoactive intestinal peptide receptor antagonist [4Cl-D-Phe6, Leu17] VIP. Am J Physiol. 1986; 250(4 Pt 1):G553-7. DOI: 10.1152/ajpgi.1986.250.4.G553. View

Granoth R, Fridkin M, Gozes I . VIP and the potent analog, stearyl-Nle(17)-VIP, induce proliferation of keratinocytes. FEBS Lett. 2000; 475(2):78-83. DOI: 10.1016/s0014-5793(00)01628-8. View

ODorisio M, Fleshman D, Qualman S, ODorisio T . Vasoactive intestinal peptide: autocrine growth factor in neuroblastoma. Regul Pept. 1992; 37(3):213-26. DOI: 10.1016/0167-0115(92)90616-3. View

Deschodt-Lanckman M, Robberecht P, Christophe J . Characterization of VIP-sensitive adenylate cyclase in guinea pig brain. FEBS Lett. 1977; 83(1):76-80. DOI: 10.1016/0014-5793(77)80645-5. View

Lutz E, Sheward W, West K, Morrow J, Fink G, Harmar A . The VIP2 receptor: molecular characterisation of a cDNA encoding a novel receptor for vasoactive intestinal peptide. FEBS Lett. 1993; 334(1):3-8. DOI: 10.1016/0014-5793(93)81668-p. View

10.

Gozes I, McCune S, Jacobson L, Warren D, Moody T, Fridkin M . An antagonist to vasoactive intestinal peptide affects cellular functions in the central nervous system. J Pharmacol Exp Ther. 1991; 257(3):959-66. View

11.

Robberecht P, Vertongen P, De Neef P, Hou X, Salmon I, Brotchi J . Expression of pituitary adenylate cyclase activating polypeptide (PACAP) receptors in human glial cell tumors. Peptides. 1994; 15(4):661-5. DOI: 10.1016/0196-9781(94)90092-2. View

12.

Pisegna J, Wank S . Molecular cloning and functional expression of the pituitary adenylate cyclase-activating polypeptide type I receptor. Proc Natl Acad Sci U S A. 1993; 90(13):6345-9. PMC: 46925. DOI: 10.1073/pnas.90.13.6345. View

13.

Sethi T, Langdon S, Smyth J, Rozengurt E . Growth of small cell lung cancer cells: stimulation by multiple neuropeptides and inhibition by broad spectrum antagonists in vitro and in vivo. Cancer Res. 1992; 52(9 Suppl):2737s-2742s. View

14.

Maruno K, Said S . Small-cell lung carcinoma: inhibition of proliferation by vasoactive intestinal peptide and helodermin and enhancement of inhibition by anti-bombesin antibody. Life Sci. 1993; 52(24):PL267-71. DOI: 10.1016/0024-3205(93)90640-o. View

15.

Journot L, Villalba M, Bockaert J . PACAP-38 protects cerebellar granule cells from apoptosis. Ann N Y Acad Sci. 1999; 865:100-10. DOI: 10.1111/j.1749-6632.1998.tb11168.x. View

16.

Etgen A, Browning E . Activators of cyclic adenosine 3':5'-monophosphate accumulation in rat hippocampal slices: action of vasoactive intestinal peptide (VIP). J Neurosci. 1983; 3(12):2487-93. PMC: 6564658. View

17.

DiCicco-Bloom E, Lu N, Pintar J, Zhang J . The PACAP ligand/receptor system regulates cerebral cortical neurogenesis. Ann N Y Acad Sci. 1999; 865:274-89. DOI: 10.1111/j.1749-6632.1998.tb11188.x. View

18.

Wollman Y, Lilling G, GOLDSTEIN M, Fridkin M, Gozes I . Vasoactive intestinal peptide: a growth promoter in neuroblastoma cells. Brain Res. 1993; 624(1-2):339-41. DOI: 10.1016/0006-8993(93)90100-2. View

19.

Ishihara T, Shigemoto R, Mori K, Takahashi K, Nagata S . Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide. Neuron. 1992; 8(4):811-9. DOI: 10.1016/0896-6273(92)90101-i. View

20.

Fishbein V, Coy D, Hocart S, Jiang N, Mrozinski Jr J, Mantey S . A chimeric VIP-PACAP analogue but not VIP pseudopeptides function as VIP receptor antagonists. Peptides. 1994; 15(1):95-100. DOI: 10.1016/0196-9781(94)90176-7. View