title: Reversal of Multidrug Resistance in Mouse Lymphoma Cells by Extracts and Flavonoids from Pistacia integerrima.
abstract: Phytochemical investigation of Pistacia integerrima has highlighted isolation of two known compounds naringenin (1) and dihydrokaempferol (2). A crude extract and these isolated compounds were here evaluated for their effects on reversion of multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). The multidrug resistance P-glycoprotein is a target for chemotherapeutic drugs from cancer cells. In the present study rhodamine- 123 exclusion screening test on human mdr1 gene transfected mouse gene transfected L5178 and L5178Y mouse T-cell lymphoma cells showed excellent MDR reversing effects in a dose dependent manner. In-silico molecular docking investigations demonstrated a common binding site for Rhodamine123, and compounds naringenin and dihydrokaempferol. Our results showed that the relative docking energies estimated by docking softwares were in satisfactory correlation with the experimental activities. Preliminary interaction profile of P-gp docked complexes were also analysed in order to understand the nature of binding modes of these compounds. Our computational investigation suggested that the compounds interactions with the hydrophobic pocket of P-gp are mainly related to the inhibitory activity. Moreover this study s a platform for the discovery of novel natural compounds from herbal origin, as inhibitor molecules against the P-glycoprotein for the treatment of cancer.
authors.affiliation: Department of Geology, University of Swabi, Ambar, Pakistan E-mail : mashaljcs@yahoo.com.
authors.forename: Abdur
authors.initials: A
authors.lastname: Rauf
authors.forename: Ghias
authors.initials: G
authors.lastname: Uddin
authors.forename: Muslim
authors.initials: M
authors.lastname: Raza
authors.forename: Bashir
authors.initials: B
authors.lastname: Ahmad
authors.forename: Noor
authors.initials: N
authors.lastname: Jehan
authors.forename: Bina S
authors.initials: BS
authors.lastname: Siddiqui
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnar
authors.forename: Akos
authors.initials: A
authors.lastname: Csonka
authors.forename: Diana
authors.initials: D
authors.lastname: Szabo
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D044950:Flavanones / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D062105:Molecular Docking Simulation / Q000379:methods; D027927:Pistacia / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D014162:Transfection / Q000379:methods
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044950:Flavanones; D005419:Flavonoids; D010936:Plant Extracts; C080220:aromadedrin; C005273:naringenin