Dicoumarol

Dicoumarol is an inhibitor of both NAD(P)H:quinone oxidoreductase 1 (NQO1) and PDK1 with IC₅₀s of 0.37 and 19.42 μM, respectively. IC50 & Target:IC50: 0.37 μM (NQO1)^[1], 19.42 μM (PDK1)^[2] In Vitro: 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]. In Vivo: Dichloroacetate (DCA) at 100 mg/kg, Dicoumarol at 30 mg/kg, and Dicoumarol at 50 mg/kg all significantly reduce tumor volume and decrease tumor weight, when compare to tumors from control or vehicle groups. Total caspase-3 and total anti-poly (ADP-ribose) polymerase (PARP) are significantly decreased in Dicoumarol-treated SKOV3 xenografts, when compare to tumors from the control or vehicle group^[2].