Quinone methide tripterine, celastrol, induces apoptosis in human myeloma cells via NF-κB pathway

  • Authors:
    • Keiichi Tozawa
    • Morihiko Sagawa
    • Masahiro Kizaki
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  • Published online on: August 17, 2011     https://doi.org/10.3892/ijo.2011.1161
  • Pages: 1117-1122
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Abstract

Multiple myeloma is still an incurable hematological malignancy despite the development of high-dose chemotherapy with stem cell transplantation. However, the therapeutic approach for multiple myeloma has progressed significantly in the last decade. Novel agents such as bortezomib, thalidomide and lenalidomide have been introduced in clinics as expanded treatment options and have improved the outcomes of patients with multiple myeloma. More recently, the development of novel agents with better effects and lower side-effects for the treatment of multiple myeloma has became necessary in the clinical setting. Celastrol is a quinone methide triterpene derived from the medicinal plant Tripterygium wilfordii, which has been used to treat chronic inflammatory and autoimmune diseases. It also has been reported that celastrol has potential as an anticancer agent; however, the effects of celastrol against myeloma have never been reported. It has been reported that the mechanisms of action occur via the NF-κB pathway. However, the effects of celastrol against multiple myeloma have never been reported. The recent clinical success of proteasome inhibitor bortezomib, which acts by inhibiting the NF-κB activity in patients with multiple myeloma led us to investigate the effects of celastrol on myeloma cells. Here we found for the first time that celastrol induces cell cycle arrest at the G1 phase followed by apoptosis in human myeloma cell line U266 cells. In addition, we showed that celastrol induces apoptosis of myeloma cells via activation of the caspase-3 and NF-κB pathways. These results suggest that celastrol would be an effective therapeutic agent in signal transduction therapy for the treatment of patients with multiple myeloma.

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November 2011
Volume 39 Issue 5

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

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Spandidos Publications style
Tozawa K, Sagawa M and Kizaki M: Quinone methide tripterine, celastrol, induces apoptosis in human myeloma cells via NF-κB pathway. Int J Oncol 39: 1117-1122, 2011
APA
Tozawa, K., Sagawa, M., & Kizaki, M. (2011). Quinone methide tripterine, celastrol, induces apoptosis in human myeloma cells via NF-κB pathway. International Journal of Oncology, 39, 1117-1122. https://doi.org/10.3892/ijo.2011.1161
MLA
Tozawa, K., Sagawa, M., Kizaki, M."Quinone methide tripterine, celastrol, induces apoptosis in human myeloma cells via NF-κB pathway". International Journal of Oncology 39.5 (2011): 1117-1122.
Chicago
Tozawa, K., Sagawa, M., Kizaki, M."Quinone methide tripterine, celastrol, induces apoptosis in human myeloma cells via NF-κB pathway". International Journal of Oncology 39, no. 5 (2011): 1117-1122. https://doi.org/10.3892/ijo.2011.1161