title: Nuclear localization of P-glycoprotein is responsible for protection of the nucleus from doxorubicin in the resistant LoVo cell line.
abstract: The high expression of P-glycoprotein (P-gp) belongs to one of the most important factors causing multidrug-resistant (MDR) of cancer cells. P-gp is primarily associated with plasma membrane; however, small fraction of that protein is present in the nuclear envelope. Such phenomenon is observed in cancer cells and may result in the selection of MDR cells as the secondary tumor and/or resistant metastasis that significantly shorten patient survival rate. Here, we confirmed nuclear localization of P-gp in resistant LoVo cells and demonstrated its impact on doxorubicin efflux from the nucleus to cytoplasm. Furthermore, we showed that P-gp located at the nuclear envelope might have a different glycoside chain when compared to the form located in the cytoplasm. It suggests that the glycoside chain plays a role in the intracellular trafficking of P-gp and may decide about the destination place in the cell.
authors.affiliation: Department of Histology and Embryology, Poznan University of Medical Sciences, H. Święcickiego 6, 60-781 Poznań, Poland. witold.szaflarski@gmail.com
authors.forename: Witold
authors.initials: W
authors.lastname: Szaflarski
authors.forename: Patrycja
authors.initials: P
authors.lastname: Sujka-Kordowska
authors.forename: Radosław
authors.initials: R
authors.lastname: Januchowski
authors.forename: Karolina
authors.initials: K
authors.lastname: Wojtowicz
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Andrzejewska
authors.forename: Michał
authors.initials: M
authors.lastname: Nowicki
authors.forename: Maciej
authors.initials: M
authors.lastname: Zabel
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004317:Doxorubicin / Q000493:pharmacokinetics*; D018432:Drug Resistance, Multiple; D006801:Humans; D009685:Nuclear Envelope / Q000378:metabolism; D021381:Protein Transport
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin
keywords: Cancer; Nuclear localization; P-glycoprotein