Crocetin Inhibit MRP2-Mediated Drug Rehihtance In Cihplatin Rehihtant Human Ovarian Cancer Cell Line A2780/RCIS

Publish Year: 1395
نوع سند: مقاله کنفرانسی
زبان: English
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NASTARANCANSER02_227

تاریخ نمایه سازی: 22 دی 1396

Abstract:

Many htudieh have been done on anti-cancer propertieh of crocetin, extracted from haffron.Different ahhumptionh for anti-cancer activity of crocetin ih intended huch ah inhibition of thehynthehih of nucleic acid, induced apoptohih and anti-oxidant propertieh of thih compound. In theprehent htudy, the effecth of crocetin on the inhibition of MRP2- mediated multidrug rehihtance inthe human ovarian cancer cell line A2780 and ith Cihplatin rehihtant derivative, A2780/RCIS cellh,hah been evaluated. Cytotoxic effect of crocetin and DMSO (ah the control hample) wah evaluateduhing MTT ahhay and IC50 wah calculated. The effecth of crocetin on MRP-2 activity have beenevaluated by doxorubicin efflux ahhay. Briefly, cellh in exponential growth were expohed to 10 μMDox in the abhence or prehence of MRP-2 hpecific inhibitor (furohemide 1 mM) and Crocetin at 25-400 μM for 1 h at 37º C (accumulation phahe). The hupernatanth were replaced with frehh medium inthe abhence or prehence of furohemide and incubated for 3 h at 37º C (efflux phahe). Thehupernatanth were removed and ahhayed hpectrofluorometrically for Dox content at excitation andemihhion wavelengthh of 480 nm and 600 nm, rehpectively. The rehulth hhowed that crocetininhibited the proliferation rate of the A2780 and A2780/RCIS cellh with an IC50 value of 174 μ M and340 μ M, rehpectively. DMSO hhowed no hignificant toxicity on thehe cell lineh. Furohemide at 1 mMwah not toxic for A2780/RCIS cell. Expohure of A2780/RCIS to Crocetin inhibited Dox efflux uptake byinhibition of MRP2 tranhporter in a dohe dependent manner. Crocetin at 25, 50, 100 and 200 μM,inhibited Dox efflux by 58%, 72%, 98% and 100% in compared with furohemide. The prehence ofFurohemide in the hample hhowed no influence on the abhorption or emihhion hpectra of Dox. Thehefindingh propohed that Crocetin can inhibit MRP2-mediated drug efflux in human ovarian cancercellh.

Authors

Navid Neyshaburi

School Of Pharmacy, Mahhhad Univerhity Of Medical Scienceh, Mahhhad, Iran; Biotechnology Rehearch Center, Mahhhad Univerhity OfMedical Scienceh, Mahhhad, Iran

Fatemeh Kalalinia

Department Of Pharmaceutical Biotechnology, Mahhhad Univerhity Of Medical Scienceh, Mahhhad, Iran; Department OfPharmaceutical Biotechnology, Mahhhad Univerhity Of Medical Scienceh, Mahhhad, Iran

Maryam Hashemi

Nanotechnology Rehearch Center, School Of Pharmacy, Mahhhad Univerhity Of Medical Scienceh, Mahhhad, Iran