Novel growth inhibitory effect of 8-Cl-cAMP is dependent on serum factors that modulate protein kinase A expression but not the hydrolysis of 8-Cl-cAMP

  • Authors:
    • A Budillon
    • T Clair
    • N Hartman
    • J Strong
    • Y Sobukawa
    • K Miki
    • A Worby
    • K Murray
    • Y Cho-Chung
  • View Affiliations

  • Published online on: December 1, 1996     https://doi.org/10.3892/ijo.9.6.1113
  • Pages: 1113-1120
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Abstract

8-Chloro-cyclic AMP (8-Cl-cAMP) exhibits growth inhibition in vitro and in vivo in a broad spectrum of cancer cell lines. We examined whether the hydrolyzed metabolite is involved in the effect of 8-Cl-cAMP. 8-Cl-cAMP (5 mu M, 3 days) exerted varying degrees (0-51%) of growth inhibition on the same cell line cultured in the medium containing different heat-inactivated serum. HPLC analysis neither detected 8-Cl-adenosine in the medium nor demonstrated any correlation between the decrease in 8-Cl-cAMP concentration in the medium and the degree of growth inhibition. The low K-m phosphodiesterase activity in the sera did not correlate with the varying degrees of growth inhibition. The cAMP-dependent protein kinase RI(alpha) subunit expression in the same cell line varied widely with the different serum supplements. 8-Cl-CAMP-, but not 8-Cl-adenosine-induced, growth inhibition correlated with the basal levels of RI(alpha) and specific downregulation of RI(alpha). 8-Cl-cAMP, but not 8-Cl-phenyl-thio-cAMP or N-6-benzyl-cAMP, inhibited cell growth in serum-free medium. These results show that 8-Cl-cAMP induces growth inhibition through down-regulation of protein kinase A type I in the absence of its hydrolysis.

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December 1996
Volume 9 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Budillon A, Clair T, Hartman N, Strong J, Sobukawa Y, Miki K, Worby A, Murray K and Cho-Chung Y: Novel growth inhibitory effect of 8-Cl-cAMP is dependent on serum factors that modulate protein kinase A expression but not the hydrolysis of 8-Cl-cAMP. Int J Oncol 9: 1113-1120, 1996
APA
Budillon, A., Clair, T., Hartman, N., Strong, J., Sobukawa, Y., Miki, K. ... Cho-Chung, Y. (1996). Novel growth inhibitory effect of 8-Cl-cAMP is dependent on serum factors that modulate protein kinase A expression but not the hydrolysis of 8-Cl-cAMP. International Journal of Oncology, 9, 1113-1120. https://doi.org/10.3892/ijo.9.6.1113
MLA
Budillon, A., Clair, T., Hartman, N., Strong, J., Sobukawa, Y., Miki, K., Worby, A., Murray, K., Cho-Chung, Y."Novel growth inhibitory effect of 8-Cl-cAMP is dependent on serum factors that modulate protein kinase A expression but not the hydrolysis of 8-Cl-cAMP". International Journal of Oncology 9.6 (1996): 1113-1120.
Chicago
Budillon, A., Clair, T., Hartman, N., Strong, J., Sobukawa, Y., Miki, K., Worby, A., Murray, K., Cho-Chung, Y."Novel growth inhibitory effect of 8-Cl-cAMP is dependent on serum factors that modulate protein kinase A expression but not the hydrolysis of 8-Cl-cAMP". International Journal of Oncology 9, no. 6 (1996): 1113-1120. https://doi.org/10.3892/ijo.9.6.1113