Screening of an annotated compound library for drug activity in a resistant myeloma cell line
2006 (English)In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 58, no 6, 749-758 p.Article in journal (Refereed) Published
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 LOPAC(1280), 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.
Place, publisher, year, edition, pages
2006. Vol. 58, no 6, 749-758 p.
anticancer drug resistance, drug screening, annotated compound library, glucocorticoids, gene expression
Medical and Health Sciences Engineering and Technology
IdentifiersURN: urn:nbn:se:uu:diva-94699DOI: 10.1007/s00280-006-0216-7ISI: 000240316700005PubMedID: 16528529OAI: oai:DiVA.org:uu-94699DiVA: diva2:168653