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. Author manuscript; available in PMC: 2013 Apr 1.
Published in final edited form as: Clin Cancer Res. 2012 Feb 20;18(7):1979–1991. doi: 10.1158/1078-0432.CCR-11-2113

Figure 4. ON 01910.Na activates the JNK pathway and upregulates the BH3-only protein NOXA.

Figure 4

A, the effect of ON 01910.Na (2 μM for 6 hours) on SAP/JNK phosphorylation, nuclear c-JUN levels, and ATF3 and NOXA expression is shown by Western blotting in two representative patients. B, summary of pSAP/JNK(n=16), nuclear c-JUN (n=5), ATF3(n=16) and NOXA (n=16) levels quantified by densitometry and normalized to γ-tubulin, β-actin or TBP is shown. The log2 of the ratio between treated and untreated cells is depicted. Statistical significance was assessed by paired Student’s T-test. C, CLL cells (CLL 24) were pretreated with NAC (25mM) for 1hr, followed by ON-01910.Na (2μM) or vehicle (DMSO) incubation for 6h additional hours. Activation of pSAP/JNK was detected by Western blotting using β-actin as loading control. D, dose response to ON 01910.Na in Jeko cells transfected with a control non-targeting shRNA vector or a vector expressing shRNAs that knockdown ATF3 or NOXA Viability by MTT assay at 48 hours normalized to vehicle control is shown. Comparison of viability at the indicated dose levels done by paired Student’s T-test (*p<0.01; **p<0.001).