Neumann, M., Wilisch, A., Diddens, H., Probst, H., Gekeler, V. (November 1992) Mdr Hamster-Cells Exhibiting Multiple Altered Gene-Expression - Effects of Dexniguldipine-Hcl (B859-35), Cyclosporine-a and Buthionine Sulfoximine. Anticancer Research, 12 (6B). pp. 2297-2302. ISSN 0250-7005
Abstract
An actinomycin D selected, multidrug-resistant (MDR) hamster CHO subline showed strong expression of the P-glycoprotein and sorcin genes together with several other alterations such as a (i) reduced growth rate, (ii) lowered topoisomerase II, (iii) lowered glutathione-S-transferase-P gene expression, and (iv) the emergence of a 15.5 kDa protein. Besides high resistances to adriamycin, actinomycin D, and vincristine, we observed a lowered sensitivity towards bleomycin, a rather hydrophilic drug usually not involved in P-glycoprotein associated MDR. Moreover, the MDR subline showed a pronounced collateral (enhanced) sensitivity towards the sterically pure dihydropyridine anticancer drug dexniguldipine-HCl (B859-35) preventing its characterization for MDR modulation here. At a non-cytotoxic dose (10 muM) the immunosuppressive cyclic peptide cyclosporin A completely abolished the resistance to vincristine, partially reversed the resistance to teniposide and strongly enhanced the sensitivity towards bleomycin, while not influencing the drug sensitivities of the parental cell line. Buthionine sulfoximine (BSO), an agent depleting cellular glutathione levels, distinctly increased the sensitivity towards teniposide at nontoxic doses (50 muM) exclusively in the MDR subline, while it did not alter vincristine or bleomycin cytotoxicity.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | BLEOMYCIN BUTHIONINE SULFOXIMINE CYCLOSPORINE-A DEXNIGULDIPINE-HCL (B859-35) GLUTATHIONE-S-TRANSFERASE-P MDR MODULATION NAD+/PROTEIN ADP-RIBOSYLTRANSFERASE P-GLYCOPROTEIN SORCIN TOPOISOMERASE II DNA TOPOISOMERASE-II MULTIDRUG-RESISTANT CELLS CHINESE-HAMSTER P-GLYCOPROTEIN BLEOMYCIN CARCINOMA TRANSFERASE INHIBITION MECHANISM SEQUENCES |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression |
| CSHL Authors: | |
| Communities: | CSHL labs |
| Depositing User: | Matt Covey |
| Date: | November 1992 |
| Date Deposited: | 01 Oct 2015 18:19 |
| Last Modified: | 01 Oct 2015 18:19 |
| URI: | https://repository.cshl.edu/id/eprint/31770 |
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