Open Access

Phosphoinositol 3-kinase, a novel target molecule for the inhibitory effects of juglone on TPA-induced cell transformation

  • Authors:
    • Jung-Il Chae
    • Jin Hyoung Cho
    • Dong Joon Kim
    • Kyung-Ae Lee
    • Moon-Kyun Cho
    • Hae-Seon Nam
    • Kee-Min Woo
    • Sang-Han Lee
    • Jung-Hyun Shim
  • View Affiliations

  • Published online on: April 10, 2012     https://doi.org/10.3892/ijmm.2012.969
  • Pages: 8-14
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Abstract

Juglone (5-hydroxy-1,4-naphthalenedione) from black walnut trees induces apoptosis and inhibits proliferation of various malignant cells. Here, we investigated whether juglone affects 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation through the phosphoinositol 3-kinase (PI3K) pathway. The results showed that TPA- and endothelial growth factor (EGF)-induced anchorage-independent colony formation were suppressed in a dose-dependent manner by treatment of JB6 CI41 mouse skin epidermal cells with juglone (2.5 and 5 µM). We demonstrated that juglone suppressed PI3K activity via direct binding to PI3K by sepharose 4B pull-down assay and western blot analysis. Juglone significantly suppressed TPA-induced protein kinase B (AKT) and c-Jun phosphorylation and c-fos activation, but not mitogen-activated protein-kinase kinase (MEK), extracellular signaling-regulated kinase (ERK) or 90 kDa ribosomal protein S6 kinase (RSK) phosphorylation. Juglone significantly blocked activator protein-1 (AP-1) and cyclooxygenase-2 (COX-2) activation more than the PI3K inhibitors LY294002 and wortmannin. Overall, these results showed the anticancer efficacy of juglone targeting PI3K to prevent TPA-induced tumorigenesis.

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July 2012
Volume 30 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Chae J, Cho JH, Kim DJ, Lee K, Cho M, Nam H, Woo K, Lee S and Shim J: Phosphoinositol 3-kinase, a novel target molecule for the inhibitory effects of juglone on TPA-induced cell transformation. Int J Mol Med 30: 8-14, 2012
APA
Chae, J., Cho, J.H., Kim, D.J., Lee, K., Cho, M., Nam, H. ... Shim, J. (2012). Phosphoinositol 3-kinase, a novel target molecule for the inhibitory effects of juglone on TPA-induced cell transformation. International Journal of Molecular Medicine, 30, 8-14. https://doi.org/10.3892/ijmm.2012.969
MLA
Chae, J., Cho, J. H., Kim, D. J., Lee, K., Cho, M., Nam, H., Woo, K., Lee, S., Shim, J."Phosphoinositol 3-kinase, a novel target molecule for the inhibitory effects of juglone on TPA-induced cell transformation". International Journal of Molecular Medicine 30.1 (2012): 8-14.
Chicago
Chae, J., Cho, J. H., Kim, D. J., Lee, K., Cho, M., Nam, H., Woo, K., Lee, S., Shim, J."Phosphoinositol 3-kinase, a novel target molecule for the inhibitory effects of juglone on TPA-induced cell transformation". International Journal of Molecular Medicine 30, no. 1 (2012): 8-14. https://doi.org/10.3892/ijmm.2012.969