title: Farnesiferol A from Ferula persica and galbanic acid from Ferula szowitsiana inhibit P-glycoprotein-mediated rhodamine efflux in breast cancer cell lines.
abstract: In multidrug resistance (MDR), cancer cells exposed to anticancer agents develop resistance to a wide variety of chemicals and chemotherapeutic agents. Sesquiterpene coumarins are reported to inhibit P-glycoprotein and/or increase cytotoxicity of anticancer drugs in P-gp-overexpressing cell lines. In the current study, we investigated the effects of galbanic acid (from the roots of Ferula szowitsiana) and farnesiferol A (from the roots of Ferula persica) on functionality of the drug transporter P-glycoprotein (P-gp) using a rhodamine 123 efflux assay in a doxorubicin resistant breast cancer cell line (MCF7/Adr). Compared to verapamil, the well-known inhibitor of P-gp, galbanic acid (5, 10, and 25 µg/mL), significantly inhibited the P-gp activity. In inhibition of the P-gp transporter, farnesiferol A (0.5 µg/mL) was more potent than verapamil at 15 min exposure. Our results indicate that the plant derived sesquiterpene coumarins, farnesiferol A and galbanic acid, may be promising candidates to be considered for further studies on the reversal of multidrug resistance phenotype in chemotherapy of cancer patients.
authors.affiliation: Biotechnology Research Center and School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohammad Yahya
authors.initials: MY
authors.lastname: Hanafi-Bojd
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Iranshahi
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mosaffa
authors.forename: Shahireh Omidvar
authors.initials: SO
authors.lastname: Tehrani
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Kalalinia
authors.forename: Javad
authors.initials: J
authors.lastname: Behravan
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport; D045744:Cell Line, Tumor; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005309:Ferula / Q000737:chemistry*; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry; D020112:Rhodamine 123 / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D003374:Coumarins; D010936:Plant Extracts; D012717:Sesquiterpenes; D020112:Rhodamine 123; C579605:farnesiferol A; C048972:galbanic acid; D014700:Verapamil