JS-K induces cytotoxicity in MM cells, but not in PBMCs and BMSCs. (A) JS-K reacts with GSH under the catalysis of GST enzymes. This reaction yields the intermediate JS-K Meisenheimer complex, which disintegrates into 4-carbethoxy-piperazi/NO and DNP-SG. Under physiologic conditions, 4-carbethoxy- piperazi/NO spontaneously generates NO^•. (B) Conventional therapy–sensitive MM.1S (♦), OPM1 (●), OPM2 (▴), and RPMI-8226 (■) MM cell lines were cultured in the presence of JS-K for 48 hours. (C) Conventional therapy–resistant cell lines MM.1R (♦; Dex-resistant), RPMI-Dox40 (●; Dox-resistant), and RPMI-LR5 (■; Mel-resistant) were cultured in the presence or absence of JS-K for 48 hours. (D) MM cells from 3 patients (solid lines; ■, ●, and ♦), PBMCs derived from 2 healthy subjects (dashed lines; ● and ▴), and BMSCs isolated from 2 patients (dashed lines; ○ and ▵) were cultured with JS-K for 72 hours. In all cases, cell viability was assessed by MTT assay, and data represent means (± SD) of triplicate cultures. The final DMSO concentration in the cultures was 0.1% or less, which was found to be nontoxic (results not shown).