Fig. 1: Statins downregulate mutant p53 proteins and exhibit cytotoxic effects in human cancer cell lines. | Cell Death & Disease

Fig. 1: Statins downregulate mutant p53 proteins and exhibit cytotoxic effects in human cancer cell lines.

From: Statin as anti-cancer therapy in autochthonous T-lymphomas expressing stabilized gain-of-function mutant p53 proteins

Fig. 1

a Simvastatin downregulates mutant but not wildtype (WT) p53, while simultaneously upregulating cleaved PARP. Immunoblot analysis of MCF7 (p53 wildtype), H358 (p53 null) and the mutp53 cancer cell lines SkBr3 (p53 R175H), MDA231 (p53 R280K), ES2 (p53 S241F, S148F), and SW480 (p53 R273H, P309S) treated with 32 μM Simvastatin for 48 h. Wildtype p53 levels in MCF7 cells are much lower than mutant levels and were probed separately with DO1 and shorter exposure. β-actin as loading control. Red asterisk indicates persistent β-actin signal from previous blotting of the same membrane, blue asterisk indicates a corresponding persistent p53 signal. This experiment was repeated in three independent experiments with similar results. b Survival of mutp53 versus control (WT and p53 null) cell lines in response to Simvastatin and Atorvastatin treatment. Dose response curves after 48 h of the indicated concentrations. CellTiter Blue viability assays of the mutant p53 lines ES2 (p53 S241F, S148F), SW480 (p53 R273H, P309S), TOV112D (p53 R175H), MDA231 (p53 R280K) and BT549 (p53 R249S) and SkBr3 (p53 R175H), compared to wildtype (MCF7) and p53 null (H358 and HCT116−/−) cells. The percent viability at endpoint of all mutant p53 lines was compared to the percent viability at endpoint of p53 null and WT lines at 32 μM Simvastatin. Unpaired Student’s t-test, ***p < 0.001, **p < 0.01. Two independent experiments were run with similar results. c Survival of mutp53 vs control cell lines after Simvastatin. Cells were treated with 32 µM Simvastatin and live cells only counted at 48 h in Cellometer Cell Counting Chambers. Unpaired Student’s t-test, ****p < 0.0001, ***p < 0.001 from three independent experiments. Error bars represent s.d. Two independent experiments were run with similar results.

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