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  • Title: Screening of an annotated compound library for drug activity in a resistant myeloma cell line.
    Author: Rickardson L, Fryknäs M, Haglund C, Lövborg H, Nygren P, Gustafsson MG, Isaksson A, Larsson R.
    Journal: Cancer Chemother Pharmacol; 2006 Dec; 58(6):749-58. PubMed ID: 16528529.
    Abstract:
    PURPOSE: Resistance to anticancer drugs is a major problem in chemotherapy. In order to identify drugs with selective cytotoxic activity in drug-resistant cancer cells, the annotated compound library LOPAC1280, containing compounds from 56 pharmacological classes, was screened in the myeloma cell line RPMI 8226 and its doxorubicin-resistant subline 8226/Dox40. METHODS: Cell survival was measured by the Fluorometric Microculture Cytotoxicity Assay. RESULTS: Selective cytotoxic activity in 8226/Dox40 was obtained for 33 compounds, with the most pronounced difference observed for the glucocorticoids. A microarray analysis of the cells showed a difference in mRNA-expression for the glucocorticoid receptor suggesting potential mechanisms for the difference in glucocorticoid sensitivity. In the presence of the glucocorticoid-receptor antagonist RU486, the sensitivity to the glucocorticoids was reduced and a similar effect level in RPMI 8226 and 8226/Dox40 was achieved. CONCLUSION: In conclusion, screening of mechanistically annotated compounds on drug-resistant cancer cells can identify compounds with selective activity and provide a basis for the development of novel treatments of drug-resistant malignancies.
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