Inhibiting AKR1C2 and 3 activities reduces preneoplastic transformation. (A and B) Formation of fluorescent coumberol from non-fluorescent coumberone (AKR1Cs substrate) in 96-well plate of senescent keratinocytes in presence of increasing concentrations of AKR1C2 inhibitor (ursodeoxycholic acid) or AKR1C3 inhibitor (3-(4-(Trifluoromethyl) phenylamino) benzoic acid). Results are shown as fold induction +/− s.d. considering 100% the AKR1Cs activities obtained upon senescence. Each condition was performed in triplicate (Student t-test; *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001). The results are representative of at least 3 independent experiments. (C and D) The emergence frequency was determined by plating cells at low density and monitoring the culture for the appearance of emergent clones as in Figure 5D. Countings were performed in triplicate (Student t-test; *p < 0.05, of the comparison of the untreated condition (0 μM) with treated conditions (0.03; 1; 3 μM)).