Knockdown of cathepsin D diminishes the potency of the chloroquine-SAHA combination and restores Trx expression. (A) siRNA knockdown of cathepsin D. Cathepsin-D–targeted or nontargeted siCONTROL siRNA were transfected into LAMA 84 CML cells using the Nucleofector II. Transfected cells were treated with 25 μM CQ, 2 μM SAHA, or the combination for 24 hours. Immunoblotting was used to evaluate the efficiency of cathepsin D knockdown. Actin served as a loading control. (B-C) Quantification of drug-induced apoptosis. LAMA 84 CML cells transfected with cathepsin D–targeted or siCONTROL siRNA were treated with 25 μM CQ, 2 μM SAHA, or the combination for 24 hours. Apoptosis was quantified by PI/FACS (B) and active caspase-3 staining (C). n = 3, error bars represent the SEM. *P < .05.