Abstract
OBJECTIVES: Crocetin, one of the main substances of saffron extract, has anti-cancer effects. Drug resistance proteins (e.g. MRP1 and MRP2) are important reasons for the failure of cancer therapy. We intended to investigate the efficacy of crocetin on MRP(1) and MRP(2) activity in human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS). MATERIALS AND METHODS: The cytotoxic effect of crocetin was evaluated by the MTT assay. The efficacy of crocetin on MRP(1) and MRP(2) expression at mRNA level was studied by real-time RT-PCR. The effect of crocetin on the activity of MRP transporters was determined by drug efflux assay. RESULTS: Crocetin decreased cell proliferation in the A2780 (IC(50): 183±7 µM) and A2780-RCIS (IC(50): 316±9 µM). Crocetin decreased the expression level of MRP1 (22±2 %) and MRP2 (48±8 %) in A2780-RCIS and inhibited MRP pumps function directly in A2780 (44±1 %) and A2780-RCIS (88±10 %) and indirectly in A2780 (32±2 %) and A2780-RCIS (48±15 %) respectively. CONCLUSION: Our findings showed that crocetin could quench drug resistance through modulation of MRP transporters in the drug resistant human ovarian cancer cells.