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. 2018 Apr 17;9(29):20265–20281. doi: 10.18632/oncotarget.24750

Figure 3. Bortezomib-resistant cSCC cells can be sensitive to MLN7243.

Figure 3

(A-C) Cells were continuously incubated with the ubiquitin E1 inhibitor MLN7243 or treated with an 8-hour MLN7243 pulse. Cell viability (live cell number), expressed as a percentage of carrier alone and the percentage of dead cells were assayed by real-time imaging 72 hours after drug addition. Values are the mean -/+ SEM of 3 independent experiments. (A) Normal keratinocytes and cSCC cell lines from RDEB patients. (B) Normal keratinocytes and cSCC cell lines from: immunocompetent (SCCIC) and transplant (SCCT) patients. (C) Relative EC50 values (μM) for reducing cell viability (live cell number) and for promoting cell death. SCCT cells and bortezomib-resistant SCCRDEBMet and SCCIC1Met cells were sensitive to death induced by MLN7243. (D) Cells were treated with carrier (-) or 0.1μM MLN7243 (+) for 12 hours and analysed by western blotting. Consistent with ubiquitin E1 inhibition MLN7243 reduced high molecular weight ubiquitin conjugates and ubiquitinated histone H2A/H2B and increased free ubiquitin.