title: Silver nanoparticles modulate ABC transporter activity and enhance chemotherapy in multidrug resistant cancer.
abstract: The emergence of multidrug resistant (MDR) cancer phenotypes dramatically attenuates the efficiency of antineoplastic drug treatments often leading to the failure of chemotherapy. Therefore there is an urgent need to engineer new therapeutically useful agents and propose innovative approaches able to defeat resistant cancer cells. Although the remarkable anti-cancer features of silver nanoparticles (AgNPs) have already been delineated their impact on MDR cancer has never been investigated. Herein, we report that AgNPs have notable anti-proliferative effect and induce apoptosis mediated cell death both in drug sensitive and in MDR cancer cells. Furthermore we show evidence that AgNPs exert an inhibitory action on the efflux activity of MDR cancer cells which feature could be exploited to enhance drug accumulation. We verified synergistic interactions of AgNPs with six different antineoplastic agents on drug resistant cells which emphasizes the excellent potential of AgNPs as combinational partners in the chemotherapy of MDR cancer.
  
  
  BACKGROUND
  The treatment of cancer often fails due to the development of multidrug resistant (MDR) cancer cells. Hence, novel approaches are being investigated to combat drug resistant cancer cells. One particular method studied here uses silver nanoparticles (AgNPs). The authors showed that AgNPs had anti-proliferative effect and ?exerted an inhibitory action on ABC transporter. The findings could suggest the possible use of AgNPs in combination with other chemotherapeutic agents in the clinical setting.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary.
authors.forename: Dávid
authors.initials: D
authors.lastname: Kovács
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Szőke
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Igaz
authors.affiliation: Department of Medical Microbiology and Immunobiology, University of Szeged, Szeged, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
authors.affiliation: Department of Medical Microbiology and Immunobiology, University of Szeged, Szeged, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Molnár
authors.affiliation: Department of Applied and Environmental Chemistry, University of Szeged, Szeged, Hungary.
authors.forename: Tímea
authors.initials: T
authors.lastname: Tóth
authors.affiliation: Department of Applied and Environmental Chemistry, University of Szeged, Szeged, Hungary.
authors.forename: Dániel
authors.initials: D
authors.lastname: Madarász
authors.affiliation: Department of Pathology, University of Szeged, Szeged, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Rázga
authors.affiliation: Department of Applied and Environmental Chemistry, University of Szeged, Szeged, Hungary; MTA-SZTE Reaction Kinetics and Surface Chemistry Research Group, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kónya
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary; Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Imre M
authors.initials: IM
authors.lastname: Boros
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary. Electronic address: kiricsim@bio.u-szeged.hu.
authors.forename: Mónika
authors.initials: M
authors.lastname: Kiricsi
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012834:Silver / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D012834:Silver
keywords: Silver nanoparticles; combinational therapy; multidrug resistance