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

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). 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