Screening of an annotated compound library for drug activity in a resistant myeloma cell line

Cancer Chemotherapy and Pharmacology
Linda RickardsonR Larsson

Abstract

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. Cell survival was measured by the Fluorometric Microculture Cytotoxicity Assay. 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. 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.

References

Jun 10, 1998·Nature·S P Williams, P B Sigler
Mar 4, 2000·Nature Genetics·U ScherfJ N Weinstein
Jun 13, 2001·Oncogene·P Herrlich
Jul 10, 2001·Acta Oncologica·P Nygren, UNKNOWN SBU-group. Swedish Council on Technology Assessment in Health Care
Mar 21, 2002·Nature Reviews. Cancer·Michael M GottesmanSusan E Bates
Oct 3, 2003·Chemistry & Biology·David E RootBrent R Stockwell
Dec 4, 2003·Brain Research. Developmental Brain Research·D Eugene RedmondRoderick V Jensen
Nov 24, 2004·Chemistry & Biology·Brian P KelleyBrent R Stockwell
Jan 1, 2005·Current Opinion in Oncology·Olga Frankfurt, Steven T Rosen
Jan 11, 2005·The Journal of Pathology·D B Longley, P G Johnston
Apr 6, 2005·Drug Discovery Today·Charles P Hart
May 7, 2005·The Journal of Steroid Biochemistry and Molecular Biology·Raj Kumar, E Brad Thompson
Jul 16, 2005·Stress : the International Journal on the Biology of Stress·B W M M PeetersG S F Ruigt

❮ Previous
Next ❯

Citations

Feb 16, 2016·Cell Chemical Biology·Nina Svensen, Samie R Jaffrey
Sep 19, 2009·Trends in Pharmacological Sciences·Matthew D HallMichael M Gottesman
May 26, 2007·Current Opinion in Chemical Biology·Anang A Shelat, R Kiplin Guy
May 15, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Grant N Wheeler, André W Brändli
Sep 14, 2011·Cancer Science·Saadia HassanPeter Nygren
Oct 10, 2006·Biochemical Pharmacology·Malin WickströmHenrik Lövborg
May 16, 2014·The Journal of Biological Chemistry·HongBin WangMarcelo G Kazanietz
Jan 9, 2007·Journal of Biomolecular Screening·Linda RickardsonHenrik Lövborg
Feb 10, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Frida PonthanJohn I Johnsen
May 23, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nikolai N KhodarevRalph R Weichselbaum
Sep 19, 2007·Molecular Cancer Therapeutics·Malin WickströmJoachim Gullbo
Mar 1, 2016·Cell·Boyang ZhaoMichael T Hemann
Oct 12, 2021·Frontiers in Cell and Developmental Biology·Pavel KatuninAnton Nikolaev

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.