Crocin suppresses multidrug resistance in mrp overexpressing ovarian cancer cell line

Shadi Mahdizadeh,1,* Gholamreza karimi,2 Javad behravan,3 Sepideh arabzadeh,4 Hermann lage,5

Abstract


Introduction

Crocin, one of the main constituents of saffron extract, has numerous biological effects such as anti-cancer effects. multidrug resistance-associated proteins 1 and 2 (mrp1 and mrp2) are important elements in the failure of cancer chemotherapy. in this study we aimed to evaluate the effects of crocin on mrp1 and mrp2 expression and function in human ovarian cancer cell line a2780 and its cisplatin-resistant derivative a2780/rcis cells.

Methods

Materials included ,fetal bovine serum (fbs) and rpmi 1640 with l-glutamine . mtt, dmso, trypan blue, doxorubicin and penicillin g/streptomycin. . crocin, rna tripure isolation kit and real-time express one-step sybr greenerâ„¢ kit . the mrp-overexpressing, cisplatinresistant ovarian cancer cell line, a2780/rcis and its parental cisplatin sensitive cell line a2780 .the cytotoxicity of crocin was assessed by the mtt assay. the effects of crocin on the mrp1 and mrp2 mrna expression and function were assessed by real-time rt-pcr and mtt assays, respectively.

Results

Our study indicated that crocin reduced cell proliferation in a dose-dependent manner in which the reduction in proliferation rate was more noticeable in the a2780 cell line compared to a2780/rcis. crocin reduced mrp1 and mrp2 gene expression at the mrna level in a2780/rcis cells. it increased doxorubicin cytotoxicity on the resistant a2780/rcis cells in comparison with the drug-sensitive a2780 cells.

Conclusion

Totally, these results indicated that crocin could suppress drug resistance via down regulation of mrp transporters in the human ovarian cancer resistant cell line.

Keywords

Mrp1, mrp2, a2780,