Bing-Mu Fang1,
Jin-Hong Jiang1,
Xue-Wu Zhang2,
Jian Fan2,
Shuang-shuang Li2,
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:- Xiang-Min Tong
Email: tongxiangmin@163.com Tel:+8657187236628
Received: 22 February 2014
Revised: 20 December 2014
Published: 28 February 2015
Citation:
Fang B, Jiang J, Zhang X, Fan J, Li S, Tong X.
Curcumin enhances bortezomib treatment of myeloma by inhibiting heat shock protein 90 expression. Trop J Pharm Res 2015; 14(2):227-233
doi:
10.4314/tjpr.v14i2.6
© 2015 The authors.
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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 effectsA288;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