The effects of crocetin, extracted from saffron, in chemotherapy against the incidence of multiple drug resistance phenotype

Objective(s): Crocetin, one of the main substances of saffron extract, has anti-cancer effects. Drug resistance proteins (e.g. MRP۱ and MRP۲) are important reasons for the failure of cancer therapy. We intended to investigate the efficacy of crocetin on MRP۱ and MRP۲ activity in human ovarian cisplatin-resistant carcinoma cell line (A۲۷۸۰-RCIS).Materials and Methods: The cytotoxic effect of crocetin was evaluated by the MTT assay. The efficacy of crocetin on MRP۱ and MRP۲ 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 A۲۷۸۰ (IC۵۰: ۱۸۳±۷ µM) and A۲۷۸۰-RCIS (IC۵۰: ۳۱۶±۹ µM). Crocetin decreased the expression level of MRP۱ (۲۲±۲ %) and MRP۲ (۴۸±۸ %) in A۲۷۸۰-RCIS and inhibited MRP pumps function directly in A۲۷۸۰ (۴۴±۱ %) and A۲۷۸۰-RCIS (۸۸±۱۰ %) and indirectly in A۲۷۸۰ (۳۲±۲ %) and A۲۷۸۰-RCIS (۴۸±۱۵ %) respectively. Conclusion: Our findings showed that crocetin could quench drug resistance through modulation of MRP transporters in the drug resistant human ovarian cancer cells.

Keywords:

A۲۷۸۰ , A۲۷۸۰-RCIS , Crocetin , MRP , Ovarian cancer cell line