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

Abstract

. 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

Modulatory effects of curcumin on heat shock proteins in cancer: A promising therapeutic approach

“…Therefore, curcumin and bortezomib demonstrated synergistic properties of MM1.R cells, inhibiting cell proliferation and increasing cellular apoptosis (which involves the regulation of the expression levels of NF-κB and HSP-90 in these cells). 99 HDAC6, HSF1, and HSPs (27,70,90) were found to be overexpressed in two different leukemia cell lines (K-562 and HL-60). With respect to normal human lymphocytes, treatment of cells with curcumin (1, 10, 25, or 50 μM) negatively modulated their expression in a dose-dependent manner.…”

“…Therefore, it was suggested that inhibition of HSP90 isoforms, with consequent activation of the apoptotic pathway, should boost the therapeutic effect of CUR3d in the liver as well as in other types of cancer . Curcumin increased myeloma cell (MM1.R line) sensitivity to bortezomib, possibly due to a decreased expression of NF‐κB and HSP90 . Another study suggested that curcumin's enhancement of both antiproliferative and proapoptotic activities of HDAC inhibitors occurs via HSP90 inhibition .…”

“…89 Curcumin increased myeloma cell (MM1.R line) sensitivity to bortezomib, possibly due to a decreased expression of NF-κB and HSP90. 90 Another study suggested that curcumin's enhancement of both antiproliferative and proapoptotic activities of HDAC inhibitors occurs via HSP90 inhibition. 91 HSP90 is a component of the IKK/NF-κB complex and is important for its activity in lymphoma cells.…”

Curcumin: A new candidate for melanoma therapy?

“…An important mediator of the cell stress response is heat shock protein 90 (Hsp90), which has been reported to be upregulated in melanoma, and its inhibition, along with the inhibition of Hsp70, has been reported to enhance the sensitivity of melanoma cells to the anti‐tumor effects of hyperthermia . Interestingly, there is evidence showing that curcumin synergistically enhances the anti‐tumor effect of bortezomib in melanoma through inhibition of Hsp90 expression . Hemeoxygenase/biliverdin reductase (HO/BVR) is another main component of the cell stress response .…”

“…60 Interestingly, there is evidence showing that curcumin synergistically enhances the anti-tumor effect of bortezomib in melanoma through inhibition of Hsp90 expression. 61 Hemeoxygenase/biliverdin reductase (HO/BVR) is another main component of the cell stress response. 62,63 This system facilitates the degradation of heme which is toxic if produced in excess or unbalanced under redox conditions.…”