Triptolide induces apoptotic cell death of multiple myeloma cells via transcriptional repression of Mcl-1

  • Authors:
    • Tomonori Nakazato
    • Morihiko Sagawa
    • Masahiro Kizaki
  • View Affiliations

  • Published online on: January 27, 2014     https://doi.org/10.3892/ijo.2014.2280
  • Pages:1131-1138
0

Abstract

Triptolide, a diterpenoid trioxide purified from the Chinese herb Tripterygium wilfordii Hook F, has been used as a natural medicine in China for hundreds of years. Several reports have demonstrated that triptolide inhibits the proliferation of cancer cells in vitro and reduces the growth of several types of tumors in vivo. To address the potential of triptolide as a novel therapeutic agent for patients with multiple myeloma, we investigated the effects of triptolide on the induction of apoptosis in human multiple myeloma cells in vitro. Triptolide rapidly induces apoptotic cell death in various myeloma cell lines. Triptolide-induced apoptosis in myeloma cells is associated with the loss of mitochondrial transmembrane potential (∆ψm), the release of cytochrome c and Smac/DIABLO from mitochondria into the cytosol, and the activation of caspase-3 and caspase-9. Furthermore, triptolide induces a rapid decline in the levels of Mcl-1 protein that correlates with caspase activation and induction of apoptosis. Inhibition of Mcl-1 synthesis by triptolide occurs at the level of mRNA transcription and is associated with an inhibition of phosphorylation of RNA polymerase II CTD. These results indicate that Mcl-1 is an important target for triptolide-induced apoptosis in myeloma cells that occurs via inhibition of Mcl-1 mRNA transcription coupled with rapid protein degradation through the ubiquitin-proteasome pathway.

Related Articles

Journal Cover

April 2014
Volume 44 Issue 4

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

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Nakazato, T., Sagawa, M., & Kizaki, M. (2014). Triptolide induces apoptotic cell death of multiple myeloma cells via transcriptional repression of Mcl-1. International Journal of Oncology, 44, 1131-1138. https://doi.org/10.3892/ijo.2014.2280
MLA
Nakazato, T., Sagawa, M., Kizaki, M."Triptolide induces apoptotic cell death of multiple myeloma cells via transcriptional repression of Mcl-1". International Journal of Oncology 44.4 (2014): 1131-1138.
Chicago
Nakazato, T., Sagawa, M., Kizaki, M."Triptolide induces apoptotic cell death of multiple myeloma cells via transcriptional repression of Mcl-1". International Journal of Oncology 44, no. 4 (2014): 1131-1138. https://doi.org/10.3892/ijo.2014.2280