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