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Modulation of Multidrug Resistance Protein 2 Efflux in the Cisplatin Resistance Human Ovarian Carcinoma Cells A2780/RCIS by Sesquiterpene Coumarins
Author(s) -
Kasaian Jamal,
Mosaffa Fatemeh,
Behravan Javad,
Masullo Milena,
Piacente Sonia,
Iranshahi Mehrdad
Publication year - 2016
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5504
Subject(s) - efflux , cisplatin , multiple drug resistance , cytotoxicity , intracellular , pharmacology , in vitro , cell culture , chemistry , sesquiterpene , ovarian carcinoma , biology , biochemistry , ovarian cancer , cancer , chemotherapy , stereochemistry , antibiotics , genetics
Recent in vitro studies showed that sesquiterpene coumarins (SCs) can be used as chemosensitizers. In this study, 14 SCs were isolated and purified from roots of four Ferula species and their structures were elucidated by spectroscopic methods. The purified SCs were evaluated for multidrug resistance (MDR) reversal properties in A2780/RCIS cells (cisplatin‐resistant derivatives of the human ovarian carcinoma cell line A2780P). Among the tested compounds, mogoltacin, mogoltadone, farnesiferol A, farnesiferol B, farnesiferol C, lehmferin, conferdione, and samarcandin showed significant MDR reversing effects. The combination of nontoxic concentrations of SCs (20 μM) with cisplatin enhanced cisplatin cytotoxicity on A2780/RCIS cells significantly. Flow cytometric efflux assay confirmed that the intracellular accumulation of 5‐carboxyfluorescein diacetate (5‐CFDA) was significantly increased in A2780/RCIS cells when treated with SCs. Our findings revealed that conferdione and samarcandin possessed the highest inhibitory effects on multidrug resistance‐associated protein 2 pump efflux, and therefore, these compounds could be considered as lead scaffolds for further structure modifications. Copyright © 2015 John Wiley & Sons, Ltd.