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Original Research Article


Curcumin Enhances Bortezomib Treatment of Myeloma by Inhibiting Heat Shock Protein 90 Expression

 

Bing-Mu Fang1, Jin-Hong Jiang1, Xue-Wu Zhang2, Jian Fan2, Shuang-shuang Li2 and Xiang-Min Tong2*

1The Lishui People’s Hospital, Lishui 324000, 2Department of Hematology, First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang 310003, PR China

 

*For correspondence: Email: tongxiangmin@163.com; Tel/Fax: 86-571-87236628

 

Received: 22 February 2014                                          Revised accepted: 20 December 2014

 

Tropical Journal of Pharmaceutical Research, February 2015; 14(2): 227-233

http://dx.doi.org/10.4314/tjpr.v14i2.6   

Abstract

 

Purpose: To investigate whether curcumin augments bortezomib-induced apoptosis in myeloma cells (MM1.R line), and to explore the molecular mechanism with regard to heat shock protein 90 (HSP90) expression.

Methods: MTT cell viability assay was used to assess growth inhibition of MM1.R cells at different concentrations of curcumin alone and also combined with 0.01 mM bortezomib. Annexin V and propidium iodide (PI) labeling were used to detect apoptosis. Caspase 3, caspase 9, NF-κB, and HSP 90 protein expression were measured by Western blotting.

Results: Curcumin alone inhibited MM1.R cell growth and increased apoptosis in a concentration-dependent manner. When curcumin was combined with low concentration (0.01 mM) bortezomib, both effects(viability inhibition and apoptosis induction increased (p < 0.05), whereas bortezomib alone had no effect (p > 0.05). Western blotting revealed that for curcumin and combined treatments, expression of the apoptotic markers, caspase 3 and caspase 9, increased while expression of NF-κB and HSP 90 decreased (p < 0.05). Again, low concentration bortezomib alone had no effect, whereas the combined treatment showed the largest effect, thus suggesting that the actions of curcumin and bortezomib are synergistic.

Conclusion: Curcumin increased MM1.R cell sensitivity to bortezomib, which may be due to suppression of NF-κB and HSP90 activity.

 

Keywords: Curcumin, Bortezomib, Myeloma cells, Cell growth, Apoptosis, Heat shock protein 90

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