Figure 4

Differential killing of mutant RAS cells by proteasome inhibitors and by topoisomerase inhibitors. (A) Bortezomib preferentially impairs viability of HCT-116 as compared to HKE-3 or HKH-2 cells across a wide range of drug concentration (top left panel). Parallel differential apoptosis induction can also be monitored, indicated by apoptosis ratios (bottom left panel) and apoptosis-induction data for individual cell lines (top right panel – relative to control vehicle treatment). Data are represented as mean ± SD. FACS analysis to monitor annexin V staining following bortezomib treatment shows preferential induction of cell death in HCT-116 cells (bottom right panel). (B) An alternative proteasome inhibitor (MG-132) also produces a preferential viability loss in HCT-116 as compared to HKE-3 or HKH-2 cells across a wide range of drug concentrations (top panel). Parallel differential apoptosis induction is indicated by apoptosis ratios (bottom panel). (C) Topotecan preferentially impairs viability of HCT-116 as compared to HKE-3 or HKH-2 cells across a wide range of drug concentration (top left panel). Parallel differential apoptosis induction can also be monitored, indicated by apoptosis ratios (bottom left panel) and apoptosis-induction data for individual cell lines (top right panel – relative to control vehicle treatment). Data are represented as mean ± SD. FACS analysis to monitor annexin V staining following topotecan treatment shows preferential induction of cell death in HCT-116 cells (bottom right panel). (D) An alternative topoisomerase inhibitor (doxorubicin) also produces a preferential viability loss in HCT-116 as compared to HKE-3 or HKH-2 cells across a wide range of drug concentrations (top panel). Parallel differential apoptosis induction is indicated by apoptosis ratios (bottom panel).