title: Small molecule inhibitors of multidrug resistance gene (MDR1) expression: preclinical evaluation and mechanisms of action.
abstract: The resistance of tumors to a number of structurally and functionally unrelated chemotherapeutic drugs has been a major obstacle for successful cancer chemotherapy. An important mechanism leading to multidrug resistance (MDR) is the overexpression of the 170 kDa P-glycoprotein (P-gp), which is a member of the ATP-binding cassette (ABC) superfamily of membrane transporters, encoded by the MDR1 gene. Aiming to overcome MDR and due to the clinical failure of P-gp inhibitors, downregulation of MDR1 expression by small molecules has been studied as a possible cancer adjuvant chemotherapy. Here we review the current knowledge on MDR1 gene expression downregulation by small molecules and the mechanisms underlying those effects observed in cancer cell lines, in an attempt to identify targets for future therapeutic interventions.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal. mapaulo@ff.ul.pt.
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Santos
authors.forename: Alexandra
authors.initials: A
authors.lastname: Paulo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D019450:Genes, MDR / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D054852:Small Molecule Libraries
chemical_list: D000970:Antineoplastic Agents; D054852:Small Molecule Libraries