Fig. 1

HHT dramatically increases bortezomib lethality and inhibits cell growth in DLBCL cells. a Various NHL cell lines SU-DHL16, SU-DHL4, SU-DHL8 (GC subtype), HBL-1, U2932 (ABC-subtype), OCI-LY18, Carnaval (double-hit) were exposed to HHT (10, 15, 12, 15, 30, 10, 10 nmol/L respectively) and bortezomib (1.5, 4, 2.5, 2, 4.5, 3, 2.5 nmol/L respectively) alone or together for 48 h, after which cell death was assessed by 7-AAD. *p < 0.05, **p < 0.01, significantly greater than values for single agent treatment. For these and subsequent studies, values represent the means ± S.D. for experiments performed in triplicate on at least 3 separate occasions. b SU-DHL16 cells were exposed to the indicated concentration of HHT in the presence or absence of bortezomib for 48 h, after which cell death was assessed by 7-AAD. c SU-DHL16 cells were exposed to the indicated concentration of bortezomib in the presence or absence of HHT for 48 h, after which cell death was assessed by 7-AAD. d SU-DHL8 cells were exposed to the indicated concentration of HHT in the presence or absence of bortezomib for 48 h, after which cell death was assessed by 7-AAD. e SU-DHL8 cells were exposed to the indicated concentration of bortezomib in the presence or absence of HHT for 48 h, after which cell death was assessed by 7-AAD. *p < 0.05, **p < 0.01, significantly greater than values for single agent treatment. f SU-DHL-8 cells were treated with a range of HHT and bortezomib concentrations administered at a fixed ratio. At the end of 48 h, the percentage of cell death was determined by monitoring 7AAD⁺ cells. CI values were determined in relation to the fractional effect by using Calcusyn software. CI values less than 1.0 correspond to synergistic interactions. g SU-DHL8 cells were treated with HHT (12 nmol/L) or bortezomib (3.5 nmol/L) individually or in combination for the indicated intervals, after which the extent of cell death was determined by 7-AAD uptake and flow cytometry. h Cells were exposed to HHT and bortezomib as described above alone or together for 48 h, after which cells were enumerated by hemocytometer (left panel, p < 0.001, significantly greater than values for single agent treatment). SU-DHL-8 were exposed to increasing concentrations of HHT and bortezomib, after which cell growth and viability were evaluated using the CellTiter-Glo Luminescent assay (right panel)