| Invitro |
Dicoumarol is an inhibitor of both NAD(P)H:quinone oxidoreductase 1 (NQO1) and PDK1 with IC50s of 0.37±0.15 and 19.42±0.032 μM, respectively. The PDK1 activity is inhibited by Dicoumarol in a dose-dependent manner. The enzymatic activity of PDK1 is reduced by approximately 94% when treated with 200 μM Dicoumarol. Dicoumarol decreases the p-PDHA1 level by 26% (100 μM Dicoumarol) and by 72% (200 μM Dicoumarol), with no statistical difference in the total PDHA1 level. Both 100 μM and 200 μM Dicoumarol markedly induce apoptosis of SKOV3 cells. Similarly, flow cytometric analysis of annexin V+PI+ cells reveals that 100 μM and 200 μM Dicoumarol treatments generate approximately 20.87% and 24.94% apoptotic cells, respectively, significantly higher than vehicle treatment[2]. It is also observed that treatment of MCF-7-TAMR cells with Dicoumarol, a known NQO1 inhibitor, reverses their tamoxifen-resistance phenotype[3]. |
