title: The influence of phenothiazine derivatives on doxorubicin treatment in sensitive and resistant human breast adenocarcinoma cells.
abstract: Breast cancer is commonly treated by various           combinations of surgery, radiation therapy,           chemotherapy and hormone therapy. Most cancers           either are increasingly resistant to any initial treatment           or acquire resistance to a broad spectrum of           anticancer drugs over time. Combination of more           than one drug or combination with multidrug resistance           (MDR) modifiers will possibly support the efficiency           of the applied therapy. Understanding the           MDR mechanisms in malignancies is crucial for developing           novel strategies for treatment. The main           goal of our study was to determine the cytostatic effect           of doxorubicin in combination with phenothiazine           derivatives (PD; promazine and triflupromazine)           in doxorubicin-sensitive (MCF-7/WT) and           -resistant (MCF-7/DOX) human breast adenocarcinoma           cell lines. We determined cytotoxicity of the           investigated compounds (MTT assay) after 24 and           48 h. The effect of phenothiazine derivatives was           evaluated and doxorubicin localization was performed           using confocal microscopy. The mode of the           cell death was examined by the comet assay. We also           determined the expression of P-glycoprotein (P-gp),           which is a membrane-associated protein responsible           for the multidrug resistance.
authors.affiliation: Internal Clinic, Regional Hospital, Lörrach, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kuzma-Richeret
authors.forename: J
authors.initials: J
authors.lastname: Saczko
authors.forename: A
authors.initials: A
authors.lastname: Choromańska
authors.forename: M
authors.initials: M
authors.lastname: Dumanska
authors.forename: M
authors.initials: M
authors.lastname: Drag-Zalesinska
authors.forename: T
authors.initials: T
authors.lastname: Wysocka
authors.forename: A
authors.initials: A
authors.lastname: Chwilkowska
authors.forename: A
authors.initials: A
authors.lastname: Pola
authors.forename: D
authors.initials: D
authors.lastname: Mosiadz
authors.forename: A
authors.initials: A
authors.lastname: Marcinkowska
authors.forename: J
authors.initials: J
authors.lastname: Kulbacka
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D020552:Comet Assay; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D010640:Phenothiazines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010640:Phenothiazines; D004317:Doxorubicin; C031637:phenothiazine