Enhancement of TPA-induced growth inhibition and apoptosis in myeloid leukemia cells by BAY 11-7082, an NF-κB inhibitor

  • Authors:
    • Annette Hansson
    • Yarí E. Marín
    • Junghan Suh
    • Arnold B. Rabson
    • Suzie Chen
    • Eliezer Huberman
    • Richard L. Chang
    • Allan H. Conney
    • Xi Zheng
  • View Affiliations

  • Published online on: October 1, 2005     https://doi.org/10.3892/ijo.27.4.941
  • Pages: 941-948
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Abstract

The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) is a potent stimulator of differentiation and apoptosis in myeloid leukemia cells. In the present study, we investigated the role of the transcription factor NF-κB in TPA-induced growth inhibition and apoptosis in the myeloid leukemia HL-60 cell line and its TPA-resistant cell variant HL-525. Unlike the parental cell line, HL-525 cells are protein kinase C (PKC)-β deficient and resistant to TPA-induced differentiation and apoptosis. We found that treatment of HL-60 cells with TPA resulted in a concentration-dependent growth inhibition and an increase in apoptotic cells. TPA only had a small effect on growth and apoptosis in HL-525 cells. Treatment of HL-60 cells with TPA (0.64-3.2 nM) caused a rapid activation of NF-κB as determined by electrophoresis mobility shift assay (EMSA) and immunocytochemistry. Although the basal level of NF-κB activity was low in HL-60 cells, TPA-resistant HL-525 cells had a high basal level of NF-κB activity. Treatment of HL-525 cells with higher concentrations of TPA (16-80 nM) resulted in a further increase in NF-κB activity. (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY 11-7082; BAY), which inhibits IκBα phosphorylation and thus decreases NF-κB activation, was found to decrease TPA-induced nuclear translocation of NF-κB. Furthermore, BAY enhanced TPA-induced growth inhibition and apoptosis in both HL-60 and HL-525 cells. Results from the present study indicate that inhibition of NF-κB by BAY was associated with enhanced TPA-induced growth inhibition and apoptosis in human myeloid leukemia cells. TPA in combination with pharmacological inhibitors of NF-κB may improve the therapeutic efficacy of TPA and overcome the resistance to TPA in some myeloid leukemia patients.

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October 2005
Volume 27 Issue 4

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

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Spandidos Publications style
Hansson A, Marín YE, Suh J, Rabson AB, Chen S, Huberman E, Chang RL, Conney AH and Zheng X: Enhancement of TPA-induced growth inhibition and apoptosis in myeloid leukemia cells by BAY 11-7082, an NF-κB inhibitor. Int J Oncol 27: 941-948, 2005.
APA
Hansson, A., Marín, Y.E., Suh, J., Rabson, A.B., Chen, S., Huberman, E. ... Zheng, X. (2005). Enhancement of TPA-induced growth inhibition and apoptosis in myeloid leukemia cells by BAY 11-7082, an NF-κB inhibitor. International Journal of Oncology, 27, 941-948. https://doi.org/10.3892/ijo.27.4.941
MLA
Hansson, A., Marín, Y. E., Suh, J., Rabson, A. B., Chen, S., Huberman, E., Chang, R. L., Conney, A. H., Zheng, X."Enhancement of TPA-induced growth inhibition and apoptosis in myeloid leukemia cells by BAY 11-7082, an NF-κB inhibitor". International Journal of Oncology 27.4 (2005): 941-948.
Chicago
Hansson, A., Marín, Y. E., Suh, J., Rabson, A. B., Chen, S., Huberman, E., Chang, R. L., Conney, A. H., Zheng, X."Enhancement of TPA-induced growth inhibition and apoptosis in myeloid leukemia cells by BAY 11-7082, an NF-κB inhibitor". International Journal of Oncology 27, no. 4 (2005): 941-948. https://doi.org/10.3892/ijo.27.4.941