Fig. 4.
Concomitant induction of telomere and mitochondrial dysfunction triggers cell death in NRAS-mutant melanoma. a NRASmut melanoma cells transduced with TERT shRNA were treated 7 days post infection with 5 µM Gamitrinib (Gam) for 48 h. Cell death was assessed by Annexin V and PI staining. b NRASmut melanoma cells and non-transformed fibroblasts were treated with 1 μM 6-thio-dG for 5 days. At day 5, culture medium was replaced and cells treated with 1 μM 6-thio-dG plus 5 μM Gam for two more days. Cells were stained with Annexin V and PI and percent cell death was determined by flow cytometry. c–e Cells were treated as in b and mitochondrial ROS levels were measured using Mitosox Red by FACS. Data represent average of three independent experiments ± SEM. p-values were calculated using unpaired Student’s t-test; *p < 0.05; ***p < 0.005