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Fig. 4 | Journal of Hematology & Oncology

Fig. 4

From: Nickel pyrithione induces apoptosis in chronic myeloid leukemia cells resistant to imatinib via both Bcr/Abl-dependent and Bcr/Abl-independent mechanisms

Fig. 4

NiPT treatment downregulates Bcr-Abl and its downstream signaling proteins. a, b NiPT decreases the protein levels of Bcr-Abl and its downstream targets. CML cells were treated with NiPT as indicated, then harvested for western blot analyses for the indicated proteins. c NiPT decreases mRNA expression of Bcr-Abl. KBM5 and KBM5R cells were exposed to 0.5 μM NiPT for 3 or 6 h. The steady state Bcr-Abl mRNA level was measured using RT2-PCR, and its expression level relative to the control was calculated. Mean ± SD (n = 3). *P < 0.05,**P < 0.01, versus control group. d NiPT inhibits cellular activity of RNA pol II. KBM5 and KBM5R cells were dose-dependently treated with NiPT, the phosphorylated and total protein levels of RNA pol II, CDK7, and CDK9 were analyzed with western blot. e Proteasome inhibition mediated caspase activation induces Bcr-Abl downregulation. KBM5 and KBM5R cells were treated with 0.5 μM NiPT for the indicated durations. The Ubs, cleaved-caspase-3, and Bcr-Abl were analyzed with western blot. Representative images are shown. f NiPT decreases Bcr-Abl and the downstream signaling proteins in a caspase-dependent manner. KBM5R cells were treated with 0.5 μM NiPT for 12 h in the absence or presence of 25 μM pan-caspase inhibitor z-VAD-fmk. b-AP15 (150 nM) was used as a positive control of proteasomal DUB inhibition. The total and phosphorylated Bcr-Abl and its downstream proteins, Ubs, PARP, caspase-3, and caspase-8 were analyzed using western blots. Representative images are shown

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