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Reversal of Multidrug Resistance in Mouse Lymphoma Cells by Extracts and Flavonoids from Pistacia integerrima

  • Rauf, Abdur (Department of Geology, University of Swabi) ;
  • Uddin, Ghias (Institute of Chemical Sciences, University of Peshawar) ;
  • Raza, Muslim (State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology) ;
  • Ahmad, Bashir (Center of Biotechnology and Microbiology, University of Peshawar) ;
  • Jehan, Noor (Department of Geology, University of Swabi) ;
  • Siddiqui, Bina S (Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi) ;
  • Molnar, Joseph (Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged) ;
  • Csonka, Akos (Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged) ;
  • Szabo, Diana (Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged)
  • Published : 2016.02.05

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.

Keywords

Pistacia integerrima;naringenin;dihydrokaempferol;multidrug resistance (MDR)

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