Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis
J. Clin. Invest. Kirsteen H. Maclean, et al. 118:79 doi:10.1172/JCI33700 [Go to this article.]

Figure 4
CQ induces hallmarks of apoptosis, yet can induce cell death independent of apoptosis. (A) CQ induces hallmarks of apoptosis in Myc-expressing MEFs. Early passage MEFs were treated for 24 h with 4-HT to activate Myc-ER^TAM and then treated with or without CQ (50 μM) for 24 h. Western blot analyses of the indicated cells demonstrated cleavage of caspase-9 and the caspase substrate PARP; asterisks indicate the specific cleavage products. (B) CQ-induced cell death is not inhibited by the broad-spectrum caspase inhibitor zVAD-fmk. Early passage MEFs were pretreated with zVAD-fmk for 1 h prior to being treated with CQ (50 μM) for 24 h. Myc-overexpressing MEFs were also pretreated with zVAD-fmk for 1 h and either serum starved (0.1%) or treated with CQ (50 μM) for a further 24 h. Viability was determined by propidium iodide staining. Results shown are the mean of 2 independent experiments. (C) CQ-induced cell death is not inhibited by Bcl-2 or Bcl-X_L. Primary bone marrow B cell cultures derived from Eμ-Myc transgenic mice were infected with MSCV-IRES-GFP, MSCV–Bcl-2–IRES-GFP or MSCV–Bcl-X_L–IRES–GFP retroviruses. GFP⁺ cells were isolated and expanded in culture and then were treated with CQ (50 μM) for 24 h. The percentage cell death was determined by staining cells with propidium iodide. By 24 h, CQ induced a 2.1-, 3.1-, or 7-fold increase in the death of GFP-, Bcl-2–, or Bcl-X_L–expressing Eμ-Myc B cells, respectively. (D) CQ induces cell death in Bax/Bak^–/– MEFs. Early passage MEFs were treated with or without CQ (50 μM) for 24 h. The percentage cell death was determined by propidium iodide incorporation. Results shown are the mean of 3 independent experiments.