Effects of proteasome inhibitor PS-341 and HSP70 inhibitor quercetin in B16F10 cell line

In this study, the morphological and cytotoxic of effects of the proteasome inhibitor PS-341, currently being used in cancer treatment, Hsp70 inhibitor quercetin and of PS-341 + quercetin combination were investigated in B16F10 melanoma cancer cell line. In our study, when different concentrations of PS-341 (1 nM, 10 nM, 50 nM, 100 nM, 1 µM and 10 µM) and quercetin (100 nM, 1 µM, 10 µM, 50 µM, 100 µM and 200 µM) were applied to B16F10 melanoma cancer cells, morphological changes were observed in PS-341-treated cells with 10 nM and higher concentrations and in quercetin-treated cells with 50 ?M and higher concentrations. Afterwards, MTT test was used to obtain % viability and then IC50 values were calculated. According to this study, the IC50 value of PS-341 was 1.3 nM and that of quercetin was 45 ?M in B16F10 cells. After these studies, PS-341 and quercetin combination was investigated to determine if a potentially novel combination therapy could be developed. Therfore, B16F10 cells were treated with DMSO (control), 10 nM PS-341, 45 ?M quercetin and 10 nM PS-341 + 45 ?M quercetin concentrations for 24 h and % viability results were compared to control and with each other. In addition, treatment of cells with DMSO (control), 100 nM PS-341, quercetin (50 ?M or 100 ?M), 100 nM PS-341 + 50 ?M quercetin or 100 nM PS-341 + 100 ?M quercetin concentrations for 24 h verified the above results. In light of these results, although singly applied inhibitor groups or combined treatment group were statistically different as compared to control, combined treatment was not statistically different than the single agent treatment. These results show that PS-341 and quercetin combination may not be more effective than the single inhibitor treatments.