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Research ArticleChemotherapy, Antibiotics, and Gene Therapy

β2-Adrenergic Receptor Agonists Inhibit the Proliferation of 1321N1 Astrocytoma Cells

L. Toll, L. Jimenez, N. Waleh, K. Jozwiak, A.Y.-H. Woo, R.-P. Xiao, M. Bernier and I. W. Wainer
Journal of Pharmacology and Experimental Therapeutics February 2011, 336 (2) 524-532; DOI: https://doi.org/10.1124/jpet.110.173971
L. Toll
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L. Jimenez
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N. Waleh
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K. Jozwiak
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A.Y.-H. Woo
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R.-P. Xiao
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M. Bernier
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I. W. Wainer
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Abstract

Astrocytomas and glioblastomas have been particularly difficult to treat and refractory to chemotherapy. However, significant evidence has been presented that demonstrates a decrease in astrocytoma cell proliferation subsequent to an increase in cAMP levels. The 1321N1 astrocytoma cell line, as well as other astrocytomas and glioblastomas, expresses β2-adrenergic receptors (β2-ARs) that are coupled to Gs activation and consequent cAMP production. Experiments were conducted to determine whether the β2-AR agonist (R,R′)-fenoterol and other β2-AR agonists could attenuate mitogenesis and, if so, by what mechanism. Receptor binding studies were conducted to characterize β2-AR found in 1321N1 and U118 cell membranes. In addition, cells were incubated with (R,R′)-fenoterol and analogs to determine their ability to stimulate intracellular cAMP accumulation and inhibit [3H]thymidine incorporation into the cells. 1321N1 cells contain significant levels of β2-AR as determined by receptor binding. (R,R′)-fenoterol and other β2-AR agonists, as well as forskolin, stimulated cAMP accumulation in a dose-dependent manner. Accumulation of cAMP induced a decrease in [3H]thymidine incorporation. There was a correlation between concentration required to stimulate cAMP accumulation and inhibit [3H]thymidine incorporation. U118 cells have a reduced number of β2-ARs and a concomitant reduction in the ability of β2-AR agonists to inhibit cell proliferation. These studies demonstrate the efficacy of β2-AR agonists for inhibition of growth of the astrocytoma cell lines. Because a significant portion of brain tumors contain β2-ARs to a greater extent than whole brain, (R,R′)-fenoterol, or some analog, may be useful in the treatment of brain tumors after biopsy to determine β2-AR expression.

Footnotes

  • This work was supported in part by funds from the National Institute on Aging Intramural Research Program, the National Institutes on Aging [Contract N01AG-3-1009], and the Foundation for Polish Science FOCUS 4/2006 Programme.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.110.173971.

  • ↵Embedded Image The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.

  • ABBREVIATIONS:

    β2-AR
    β2-adrenergic receptor
    PBS
    phosphate-buffered saline
    HEK
    human embryonic kidney
    ICI 118-551
    erythro-dl-1(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol
    CGP-12177
    4-[3-[(1,1-dimethylethyl)amino]2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one
    PKA
    protein kinase A
    H-89
    N-[2-[[3-(4-bromophenyl)-2-propen-1-yl]amino]ethyl]5-isoquinolinesulfonamide
    ERK
    extracellular signal-regulated kinase.

  • Received August 12, 2010.
  • Accepted November 1, 2010.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 384 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 384, Issue 2
1 Feb 2023
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Research ArticleChemotherapy, Antibiotics, and Gene Therapy

β2-Adrenergic Receptor Agonists Inhibit the Proliferation of 1321N1 Astrocytoma Cells

L. Toll, L. Jimenez, N. Waleh, K. Jozwiak, A.Y.-H. Woo, R.-P. Xiao, M. Bernier and I. W. Wainer
Journal of Pharmacology and Experimental Therapeutics February 1, 2011, 336 (2) 524-532; DOI: https://doi.org/10.1124/jpet.110.173971

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Research ArticleChemotherapy, Antibiotics, and Gene Therapy

β2-Adrenergic Receptor Agonists Inhibit the Proliferation of 1321N1 Astrocytoma Cells

L. Toll, L. Jimenez, N. Waleh, K. Jozwiak, A.Y.-H. Woo, R.-P. Xiao, M. Bernier and I. W. Wainer
Journal of Pharmacology and Experimental Therapeutics February 1, 2011, 336 (2) 524-532; DOI: https://doi.org/10.1124/jpet.110.173971
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