Epifriedelanol enhances adriamycin-induced cytotoxicity towards K562/ADM cells by down regulating of P-gp and MRP2

1. Multidrug resistance (MDR) is a critical issue during chemotherapy of cancers. Epifriedelanol (Epi) is the effective compounds from the Root Bark of Ulmus davidiana. This study aims to investigate the effect of Epi on MDR and its potential mechanism in the adriamycin (Adr)-resistant K562/ADM cells.2. The effect of Epi on MDR, P-glycoprotein (P-gp) and multidrug resistance-associated proteins (MRPs) were investigated in the adriamycin (Adr)-resistant K562/ADM cells. In addition, the alterations of nuclear receptor pregnane X receptor (PXR) and constitutive androstane receptor (CAR) mRNA expression levels in K562/ADM cells after Epi treatment were also examined.3. Epi significantly enhanced Adr-induced cytotoxicity towards K562/ADM cells. Combination of Epi and Adr can significantly reduce the 50% inhibitory concentration (IC₅₀) of K562/ADM cells to Adr. The reversal fold was 1.83 and 3.64 after treated with Epi at 10 and 20 μM, respectively. The intracellular accumulation of Adr was significant increased after exposure to Epi at 5-20 μM compared with the control group. Furthermore, Epi treatment significantly decreased the mRNA and protein expression of P-gp and MRP2 in K562/ADM cells.4. The present study demonstrated that Epi could enhance Adr-induced cytotoxicity towards K562/ADM cells accompanied by the down-regulation of P-gp and MRP2.