The induction of apoptosis by a combined 1,25(OH)2D3 analog, EB1089 and TGF-β1 in NCI-H929 multiple myeloma cells

  • Authors:
    • Woo Hyun Park
    • Jae Goo Seol
    • Eun Shil Kim
    • Lise Binderup
    • H. Phillip Koeffler
    • Byoung Kook Kim
    • Young Yiul Lee
  • View Affiliations

  • Published online on: March 1, 2002     https://doi.org/10.3892/ijo.20.3.533
  • Pages: 533-542
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Abstract

Previously, we reported that EB1089 inhibited the growth of NCI-H929 myeloma cells via cell cycle arrest and apoptosis. In the present study, we investigated whether a combined EB1089 and TGF-β1 synergistically inhibited the cell proliferation of myeloma cell lines. While TGF-β1 alone could not inhibit the proliferation of any of the tested myeloma cells, synergistic effect between EB1089 (1x10-8 M) and TGF-β1 (1 ng/ml) was observed in NCI-H929 cells. TGF-β1 intensified the decreased expression of CDK2, CDK4, CDK6 and cyclin D1 in EB1089-treated NCI-H929 cells. However, these effects did not intensify to decrease CDK2 activity of EB1089-treated NCI-H929 cells, resulting in no difference in the extent of G1 arrest between EB1089- and both agents-treated cells. Remarkably, both agents synergistically induce apoptosis of NCI-H929 cells, which was accompanied with up-regulation of Bax, degradation of PARP and Rb proteins, and loss of mitochondrial transmembrane potential (Δψm). EB1089 caused the induction of SMAD4, a mediator of TGF-β1 signaling. In addition, a combined EB1089 and TGF-β1 increased p21 and JNK/SAPK activity whereas neither EB1089 nor TGF-β1 affected p21 and JNK/SAPK activity. Taken together, these results suggest that treatment with both EB1089 and TGF-β1 synergistically inhibits the proliferation of NCI-H929 cells through apoptosis.

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March 2002
Volume 20 Issue 3

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

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Spandidos Publications style
Park WH, Seol JG, Kim ES, Binderup L, Koeffler HP, Kim BK and Lee YY: The induction of apoptosis by a combined 1,25(OH)2D3 analog, EB1089 and TGF-β1 in NCI-H929 multiple myeloma cells. Int J Oncol 20: 533-542, 2002
APA
Park, W.H., Seol, J.G., Kim, E.S., Binderup, L., Koeffler, H.P., Kim, B.K., & Lee, Y.Y. (2002). The induction of apoptosis by a combined 1,25(OH)2D3 analog, EB1089 and TGF-β1 in NCI-H929 multiple myeloma cells. International Journal of Oncology, 20, 533-542. https://doi.org/10.3892/ijo.20.3.533
MLA
Park, W. H., Seol, J. G., Kim, E. S., Binderup, L., Koeffler, H. P., Kim, B. K., Lee, Y. Y."The induction of apoptosis by a combined 1,25(OH)2D3 analog, EB1089 and TGF-β1 in NCI-H929 multiple myeloma cells". International Journal of Oncology 20.3 (2002): 533-542.
Chicago
Park, W. H., Seol, J. G., Kim, E. S., Binderup, L., Koeffler, H. P., Kim, B. K., Lee, Y. Y."The induction of apoptosis by a combined 1,25(OH)2D3 analog, EB1089 and TGF-β1 in NCI-H929 multiple myeloma cells". International Journal of Oncology 20, no. 3 (2002): 533-542. https://doi.org/10.3892/ijo.20.3.533