Inhibition of NF-κB by (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY11-7082; BAY) is associated with enhanced 12-O-tetradecanoylphorbol-13-acetate-induced growth suppression and apoptosis in human prostate cancer PC-3 cells

  • Authors:
    • Xi Zheng
    • Richard L. Chang
    • Xiao-Xing Cui
    • Gina Avila
    • Mou-Tuan Huang
    • Yue Liu
    • Ah Ng Tony Kong
    • Arnold B. Rabson
    • Allan H. Conney
  • View Affiliations

  • Published online on: January 1, 2008     https://doi.org/10.3892/ijo.32.1.257
  • Pages: 257-264
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Abstract

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) alone or in combination with an NF-κB inhibitor, (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY 11-7082; BAY), on the growth and apoptosis of human prostate cancer PC-3 cells cultured in vitro or grown in immunodeficient mice were studied. Treatment of cultured PC-3 cells with TPA (0.2-10 ng/ml) for 96 h resulted in growth inhibition and apoptosis in a concentration-dependent manner. BAY inhibited NF-κB activity in PC-3 cells as determined by a luciferase reporter assay and enhanced TPA-induced growth inhibition and apoptosis in cultured PC-3 cells. In animal studies, NCr immunodeficient mice were injected subcutaneously with PC-3 cells in Matrigel. Mice with well-established tumors received daily i.p. injections with TPA (100 ng/g body weight/day), BAY (4 µg/g/day), or a combination of TPA (100 ng/g/day) and BAY (4 µg/g/day) for 36 days. Tumor growth occurred in all of the vehicle-treated control mice. The percent of animals with some tumor regression after 36 days of treatment was 0% for the control group, 40% for the TPA group, 50% for the BAY group and 100% for the TPA + BAY group. Mechanistic studies indicated that treatment of the mice with TPA or TPA + BAY decreased proliferation and increased apoptosis in the tumors. Results from our studies indicate that inhibition of NF-κB activity is associated with enhanced TPA-induced growth inhibition and apoptosis in PC-3 cells. Inhibition of NF-κB activity by suitable pharmacological inhibitors may be an effective strategy for improving the therapeutic efficacy of TPA in prostate cancer.

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January 2008
Volume 32 Issue 1

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

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Spandidos Publications style
Zheng X, Chang RL, Cui X, Avila G, Huang M, Liu Y, Kong AN, Rabson AB and Conney AH: Inhibition of NF-κB by (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY11-7082; BAY) is associated with enhanced 12-O-tetradecanoylphorbol-13-acetate-induced growth suppression and apoptosis in human prostate cancer PC-3 cells. Int J Oncol 32: 257-264, 2008
APA
Zheng, X., Chang, R.L., Cui, X., Avila, G., Huang, M., Liu, Y. ... Conney, A.H. (2008). Inhibition of NF-κB by (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY11-7082; BAY) is associated with enhanced 12-O-tetradecanoylphorbol-13-acetate-induced growth suppression and apoptosis in human prostate cancer PC-3 cells. International Journal of Oncology, 32, 257-264. https://doi.org/10.3892/ijo.32.1.257
MLA
Zheng, X., Chang, R. L., Cui, X., Avila, G., Huang, M., Liu, Y., Kong, A. N., Rabson, A. B., Conney, A. H."Inhibition of NF-κB by (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY11-7082; BAY) is associated with enhanced 12-O-tetradecanoylphorbol-13-acetate-induced growth suppression and apoptosis in human prostate cancer PC-3 cells". International Journal of Oncology 32.1 (2008): 257-264.
Chicago
Zheng, X., Chang, R. L., Cui, X., Avila, G., Huang, M., Liu, Y., Kong, A. N., Rabson, A. B., Conney, A. H."Inhibition of NF-κB by (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY11-7082; BAY) is associated with enhanced 12-O-tetradecanoylphorbol-13-acetate-induced growth suppression and apoptosis in human prostate cancer PC-3 cells". International Journal of Oncology 32, no. 1 (2008): 257-264. https://doi.org/10.3892/ijo.32.1.257