title: A new generation of MDR modulating agents with dual activity: P-gp inhibitor and iNOS inducer agents.
abstract: MultiDrug Resistance (MDR) is due to the ability of some ATPase transporters to efflux chemotherapeutic agents out from tumor cells decreasing the endocellular concentration for the pharmacological effect, causing cancer cells chemoresistance. In the present work, a set of MDR modulating agents (MC89, MC70, PB28, IG9) able to modulate transmembrane ATP-dependent transporter, P-glycoprotein (P-gp), and also to induce inducible nitric oxide synthase (iNOS) expression in a panel of tumor cell lines are presented. All selected compounds, known as potent P-gp modulating agents, stimulated nitric oxide (NO) via iNOS in U937, Caco-2 and MCF7-Adr cell lines. The results displayed a new pharmacological strategy to revert MDR and lead to develop a new class of MDR reverting agents devoid of the limits of P-gp inhibitors third generation.
authors.affiliation: Dipartimento Farmacochimico, Università degli Studi di Bari, Bari, Italy. colabufo@farmchim.uniba.it
authors.forename: Nicola Antonio
authors.initials: NA
authors.lastname: Colabufo
authors.forename: Marialessandra
authors.initials: M
authors.lastname: Contino
authors.forename: Francesco
authors.initials: F
authors.lastname: Berardi
authors.forename: Roberto
authors.initials: R
authors.lastname: Perrone
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Panaro
authors.forename: Antonia
authors.initials: A
authors.lastname: Cianciulli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mitolo
authors.forename: Amalia
authors.initials: A
authors.lastname: Azzariti
authors.forename: Annelisa
authors.initials: A
authors.lastname: Quatrale
authors.forename: Angelo
authors.initials: A
authors.lastname: Paradiso
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II