Figure 1.

High concentrations of metformin and EVP 4593 reduce proliferation of cancer cells lacking CI. (a–c) Proliferation of SKOV3^−/−, HCT116^−/− and B16-F10^−/− cells upon treatment with different concentrations of metformin (METF) (a), EVP 4593 (EVP) (b) and BAY 87-2243 (BAY) (c). Data are shown as cell confluence ratio of treated (T) to untreated (UT) control cells after 24, 48 and 72 h of incubation with the indicated compound concentrations. Cell confluence was determined by using the Incucyte Live-imaging System and at each time point was normalized on time 0 (T0). Data are mean ± s.e.m. (n ≥ 3) and one-sample t-test was performed for each treatment using 100 as reference value. Statistical significance is specified with asterisks (*p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001). (d) CI-independent antiproliferative effect for each compound concentration in SKOV3^−/−, HCT116^−/− and B16-F10^−/− cell lines at 72 h of inhibitor treatment. Data (mean ± s.e.m., n ≥ 3) are expressed as [100% (UT) – cell confluence ratio (T/UT %)] and one-sample t-test was performed for each treatment using 0 as reference value. Statistical significance is specified with asterisks (*p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001).