Triptolide overcomes dexamethasone resistance and enhanced PS-341-induced apoptosis via PI3k/Akt/NF-κB pathways in human multiple myeloma cells

  • Authors:
    • Min Yang
    • Jian Huang
    • Han-zhang Pan
    • Jie Jin
  • View Affiliations

  • Published online on: October 1, 2008     https://doi.org/10.3892/ijmm_00000047
  • Pages: 489-496
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Abstract

Human multiple myeloma is a presently incurable hematological malignancy and novel biologically based therapies are urgently needed. Triptolide (TPL) is a purified diterpenod isolated from the Chinese herb, Tripterygium wilfordii Hook. F that has shown antitumor activities in various cancer cell types. But its activity in Dex-resistant multiple myeloma cell lines and the main upstream signaling pathway has not been reported. Here we show that TPL induces apoptosis in dexamethasone-sensitive (MM.1S) and dexamethasone-resistant (MM.1R) cells, most importantly its main upstream signaling pathway is through the PI3k/Akt/NF-κB pathway and is also associated with MAPK pathway, via mitochondrial apoptotic signaling and is also associated with the caspase and Bcl-2 family members. Moreover, TPL was able to enhance the activities of dexamethasone or bortezomib/PS-341 in multiple myeloma cell lines. Collectively, these findings provide the framework for a clinical evaluation of TPL, either alone or in combination with dexamethasone or bortezomib/PS-341, to overcome drug resistance and improve outcome for patients with this universially fatal hematological malignancy.

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October 2008
Volume 22 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yang M, Huang J, Pan H and Jin J: Triptolide overcomes dexamethasone resistance and enhanced PS-341-induced apoptosis via PI3k/Akt/NF-κB pathways in human multiple myeloma cells. Int J Mol Med 22: 489-496, 2008.
APA
Yang, M., Huang, J., Pan, H., & Jin, J. (2008). Triptolide overcomes dexamethasone resistance and enhanced PS-341-induced apoptosis via PI3k/Akt/NF-κB pathways in human multiple myeloma cells. International Journal of Molecular Medicine, 22, 489-496. https://doi.org/10.3892/ijmm_00000047
MLA
Yang, M., Huang, J., Pan, H., Jin, J."Triptolide overcomes dexamethasone resistance and enhanced PS-341-induced apoptosis via PI3k/Akt/NF-κB pathways in human multiple myeloma cells". International Journal of Molecular Medicine 22.4 (2008): 489-496.
Chicago
Yang, M., Huang, J., Pan, H., Jin, J."Triptolide overcomes dexamethasone resistance and enhanced PS-341-induced apoptosis via PI3k/Akt/NF-κB pathways in human multiple myeloma cells". International Journal of Molecular Medicine 22, no. 4 (2008): 489-496. https://doi.org/10.3892/ijmm_00000047