Biomaterial Database

Cyclosporin A and verapamil enhancement of daunorubicin-produced nucleolar protein B23 translocation in daunorubicin-resistant and -sensitive human and murine tumor cells. 1989

P Sweet, and P K Chan, and L M Slater

Department of Medicine, California College of Medicine, University of California, Irvine 92717.

It has recently been shown that anthracycline antibiotic-resistant tumor cells are less responsive to daunorubicin-stimulated B23 nucleolar phosphoprotein translocation than drug-sensitive cells. Since cyclosporin A and verapamil reverse primary acquired and secondary cross-resistance to daunorubicin, we investigated the effect of these agents on nucleolar B23 translocation in sensitive and resistant tumors. We compared modified to baseline B23 phosphoprotein distribution between predominantly nucleolar, mixed nucleolar-nuclear, or nuclear immunofluorescence using a monoclonal anti-B23 antibody in parental drug-sensitive and multidrug-resistant acute lymphatic leukemia and in daunorubicin-sensitive and -resistant murine hepatoma. Our experiments show that cyclosporin A and verapamil alone have no effect on B23 phosphoprotein translocation, but that the addition of either agent to sensitive parental or resistant tumor sublines markedly enhances daunorubicin-stimulated translocation. This effect correlates with the correction of impaired daunorubicin inhibition of RNA synthesis by cyclosporin A and verapamil in the resistant sublines. Our observations suggest that nucleolar B23 phosphoprotein is an important site in the modulation of anthracycline antibiotic antitumor activity.

UI	MeSH Term	Description	Entries
D008114	Liver Neoplasms, Experimental	Experimentally induced tumors of the LIVER.	Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D009687	Nuclear Proteins	Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.	Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D003524	Cyclosporins	A group of closely related cyclic undecapeptides from the fungi Trichoderma polysporum and Cylindocarpon lucidum. They have some antineoplastic and antifungal action and significant immunosuppressive effects. Cyclosporins have been proposed as adjuvants in tissue and organ transplantation to suppress graft rejection.	Cyclosporines
D003630	Daunorubicin	A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.	Daunomycin,Rubidomycin,Rubomycin,Cerubidine,Dauno-Rubidomycine,Daunoblastin,Daunoblastine,Daunorubicin Hydrochloride,NSC-82151,Dauno Rubidomycine,Hydrochloride, Daunorubicin,NSC 82151,NSC82151
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000090243	Nucleophosmin	Predominantly localized in the CELL NUCLEOLUS, involved in diverse cellular processes such as ribosome biogenesis, cytoplasmic-nuclear trafficking, centrosome duplication, and regulation of p53.	NO38 Protein,Nucleolar Phosphoprotein B23,Nucleolar Protein B23,Nucleophosmid,Numatrin,Phosphoprotein B23, Nucleolus,Protein B23,B23, Nucleolar Phosphoprotein,B23, Nucleolar Protein,B23, Nucleolus Phosphoprotein,B23, Protein,Nucleolus Phosphoprotein B23,Phosphoprotein B23, Nucleolar,Protein B23, Nucleolar,Protein, NO38
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014700	Verapamil	A calcium channel blocker that is a class IV anti-arrhythmia agent.	Iproveratril,Calan,Cordilox,Dexverapamil,Falicard,Finoptin,Isoptin,Isoptine,Izoptin,Lekoptin,Verapamil Hydrochloride,Hydrochloride, Verapamil