title: Reversal of P-glycoprotein-mediated multidrug resistance in MCF-7/Adr cancer cells by sesquiterpene coumarins.
abstract: In the present study, fifteen sesquiterpene coumarins were isolated and purified from different Ferula species, and were tested for their MDR reversal properties. Enhancement of doxorubicin cytotoxicity in MCF-7/Adr cells (doxorubicin resistant derivatives of MCF-7 cells overexpressing P-gp), when combined with very non-toxic concentrations of the sesquiterpene coumarins (50 μM) including umbelliprenin, farnesiferol B, farnesiferol C and lehmferin, proved significant MDR reversal activity of these coumarins. Flow cytometric efflux assay confirmed that the intracellular accumulation of Rho123 was significantly increased in MCF-7/Adr cells when treated with sesquiterpene coumarins. A deeper insight into the structure-activity relationship of sesquiterpene coumarins revealed that ring-opened drimane-type sesquiterpene coumarins including farnesiferol B, farnesiferol C and lehmferin possessed the best inhibitory effects on P-gp pump efflux and they could be considered as lead scaffolds for further structure modifications.
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Jamal
authors.initials: J
authors.lastname: Kasaian
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mosaffa
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Behravan
authors.affiliation: Dipartimento di Farmacia, Universita' degli Studi di Salerno, Via Giovanni Paolo II, 84084 Salerno, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Masullo
authors.affiliation: Dipartimento di Farmacia, Universita' degli Studi di Salerno, Via Giovanni Paolo II, 84084 Salerno, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Piacente
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Ghandadi
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Iranshahim@mums.ac.ir.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Iranshahi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D003374:Coumarins / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005309:Ferula / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D015394:Molecular Structure; D018517:Plant Roots / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003374:Coumarins; D004317:Doxorubicin
keywords: Antiproliferation; Cancer; Multidrug resistance; P-gp; Sesquiterpene coumarins