title: Selenoesters and selenoanhydrides as novel multidrug resistance reversing agents: A confirmation study in a colon cancer MDR cell line.
abstract: Taking into account that multidrug resistance (MDR) is the main cause for chemotherapeutic failure in cancer treatment and as a continuation of our efforts to overcome this problem we report the evaluation of one cyclic selenoanhydride (1) and ten selenoesters (2-11) in MDR human colon adenocarcinoma Colo 320 cell line. The most potent derivatives (1, 9-11) inhibited the ABCB1 efflux pump much stronger than the reference compound verapamil. Particularly, the best one (9) was 4-fold more potent than verapamil at a 10-fold lower concentration. Furthermore, the evaluated derivatives exerted a potent and selective cytotoxic activity. In addition, they were strong apoptosis inducers as the four derivatives triggered apoptotic events in a 64-72% of the examined MDR Colo 320 human adenocarcinoma cells.
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Dóm tér 10, 6720 Szeged, Hungary.
authors.forename: Márió
authors.initials: M
authors.lastname: Gajdács
authors.affiliation: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Dóm tér 10, 6720 Szeged, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, School of Pharmacy, University of Navarra, Irunlarrea 1, 31010 Pamplona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sanmartín
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Małgorzata Anna
authors.initials: MA
authors.lastname: Marć
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Handzlik
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, School of Pharmacy, University of Navarra, Irunlarrea 1, 31010 Pamplona, Spain; Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland. Electronic address: enriquedominguezalv@gmail.com.
authors.forename: Enrique
authors.initials: E
authors.lastname: Domínguez-Álvarez
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000812:Anhydrides / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004952:Esters / Q000737:chemistry*; D006801:Humans; D016566:Organoselenium Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014700:Verapamil / Q000378:metabolism / Q000494:pharmacology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000812:Anhydrides; D000970:Antineoplastic Agents; D004952:Esters; D016566:Organoselenium Compounds; D014700:Verapamil
keywords: ABCB1 efflux pump (P-glycoprotein); Apoptosis; Cancer; MDR efflux pumps; Multidrug resistance (MDR); Selenium; Selenoesters