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International Journal of Molecular Medicine
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Print ISSN: 1107-3756 Online ISSN: 1791-244X
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July 2012 Volume 30 Issue 1

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International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

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International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

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Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

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Article 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 / Copyright

    Affiliations: Department of Oral Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Project, Chonbuk National University, Jeonju, Republic of Korea, Hormel Institute, University of Minnesota, Austin, MN 55912, USA, Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 330-090, Republic of Korea, Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 330-090, Republic of Korea
  • Pages: 8-14
    |
    Published online on: April 10, 2012
       https://doi.org/10.3892/ijmm.2012.969
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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