A high density assay format for the detection of novel cytotoxic agents in large chemical libraries Journal Article
| Authors: | Shum, D.; Radu, C.; Kim, E.; Cajuste, M.; Shao, Y.; Seshan, V. E.; Djaballah, H. |
| Article Title: | A high density assay format for the detection of novel cytotoxic agents in large chemical libraries |
| Abstract: | In response to the need for inexpensive high throughput assays for anti-cancer drug screening, a 1536-well microtiter plate based assay utilizing the Alamar Blue fluorescent dye as a measure of cellular growth was validated in 10 μL assay volume. Its robustness was assessed in a screen against a library of 2000 known bioactives; with an overall Z′ value of 0.89 for assay robustness, several known cytotoxic agents were identified including and not limited to anthracyclines, cardiac glycosides, gamboges, and quinones. To further test the sensitivity of the assay, IC50 determinations were performed in both 384-well and 1536-well formats and the obtained results show a very good correlation between the two density formats. These findings demonstrate that this newly developed assay is simple to set up, robust, highly sensitive and inexpensive. It could potentially provide a rapid way to screen established and primary tumor cell lines against large chemical libraries. |
| Keywords: | controlled study; human cell; cytotoxic agent; doxorubicin; paclitaxel; antineoplastic agent; cell proliferation; cell viability; unindexed drug; cell growth; fluorescence; fluorescent dye; cell line; cardiac glycoside; digoxigenin; digoxin; gambogic acid; ouabain; peruvoside; phenylmercuric acetate; pyrithione zinc; antineoplastic activity; cytotoxicity; drug structure; high throughput screening; small molecule libraries; assay; cancer inhibition; screening; tumor cell line; quinone derivative; molecular structure; anthracycline derivative; ic 50; structure analysis; inhibitory concentration 50; anthracyclines; drug determination; drug sensitivity; antiangiogenic activity; combinatorial chemistry; miniaturization; drug identification; cytochalasin a; cycloheximide; staurosporine; crystal violet; hts; cymarin; 8 quinolinol; nceb1; resazurin; digitoxin; ethidium bromide; forskolin; oxyphenbutazone; pristimerin; puromycin; thiomersal; tomatine; microtiter plate assay |
| Journal Title: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Volume: | 23 |
| Issue: | 6 |
| ISSN: | 1475-6366 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2008-12-01 |
| Start Page: | 931 |
| End Page: | 945 |
| Language: | English |
| DOI: | 10.1080/14756360701810082 |
| PUBMED: | 18608772 |
| PROVIDER: | scopus |
| PMCID: | PMC3710589 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "CODEN: JEIMA" - "Source: Scopus" |
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