Synergistic stimulatory effect of 12-O-tetradecanoylphorbol-13-acetate and capsaicin on macrophage differentiation in HL-60 and HL-525 human myeloid leukemia cells

  • Authors:
    • Xi Zheng
    • Amanda Ryan
    • Namrata Patel
    • Stephanie Klemons
    • Annette Hansson
    • Weichung Joe Shih
    • Yong Lin
    • Eliezer Huberman
    • Richard L. Chang
    • Allan H. Conney
  • View Affiliations

  • Published online on: February 1, 2005     https://doi.org/10.3892/ijo.26.2.441
  • Pages: 441-448
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Abstract

Our previous studies demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) had pharmacological activity for the treatment of myeloid leukemia patients. In the present study, we investigated the effects of TPA alone or in combination with capsaicin (8-methyl-N-vanillyl-6-nonenamide) on growth and differentiation in myeloid leukemia HL-60 cells and in a TPA-resistant HL-60 variant cell line termed HL-525. Treatment of HL-60 cells with TPA (0.16-1.6 nM) for 48 h resulted in concentration-dependent growth inhibition and cell differentiation (via the macrophage pathway). Capsaicin (5-50 µM) inhibited the growth of HL-60 cells in a concentration-dependent manner. Treatment of HL-60 cells with capsaicin alone only resulted in a small increase in the number of differentiated cells but treatment of the cells with TPA in combination with capsaicin synergistically increased differentiation. Moreover, inhibitors of protein kinase C (PKC), 7-hydroxystaurosporin (UCN-01; 100 nM) and chelerythrine (0.5 µM), significantly decreased HL-60 cell differentiation induced by the combination of TPA and capsaicin. These results suggest that PKC may be involved in HL-60 cell differentiation induced by TPA in combination with capsaicin. Capsaicin alone caused a very small increase in differentiation in the TPA-resistant HL-525 cells. However, treatment of HL-525 cells with combinations of TPA (0.16 nM) and capsaicin (10-50 µM) caused a strong synergistic increase in differentiation. Results from the present study suggest that a combination of TPA and capsaicin may improve the therapeutic efficacy of TPA and overcome resistance to TPA in some myeloid leukemia patients.

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February 2005
Volume 26 Issue 2

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

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APA
Zheng, X., Ryan, A., Patel, N., Klemons, S., Hansson, A., Shih, W.J. ... Conney, A.H. (2005). Synergistic stimulatory effect of 12-O-tetradecanoylphorbol-13-acetate and capsaicin on macrophage differentiation in HL-60 and HL-525 human myeloid leukemia cells. International Journal of Oncology, 26, 441-448. https://doi.org/10.3892/ijo.26.2.441
MLA
Zheng, X., Ryan, A., Patel, N., Klemons, S., Hansson, A., Shih, W. J., Lin, Y., Huberman, E., Chang, R. L., Conney, A. H."Synergistic stimulatory effect of 12-O-tetradecanoylphorbol-13-acetate and capsaicin on macrophage differentiation in HL-60 and HL-525 human myeloid leukemia cells". International Journal of Oncology 26.2 (2005): 441-448.
Chicago
Zheng, X., Ryan, A., Patel, N., Klemons, S., Hansson, A., Shih, W. J., Lin, Y., Huberman, E., Chang, R. L., Conney, A. H."Synergistic stimulatory effect of 12-O-tetradecanoylphorbol-13-acetate and capsaicin on macrophage differentiation in HL-60 and HL-525 human myeloid leukemia cells". International Journal of Oncology 26, no. 2 (2005): 441-448. https://doi.org/10.3892/ijo.26.2.441