Screening Assay for Promigratory/Antimigratory Compounds

• Published in: Analytical biochemistry Vol. 280; no. 1; pp. 11 - 19
• Main Authors: Rust, Will L., Huff, Janice L., Plopper, George E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.04.2000
• Subjects: Antineoplastic Agents - pharmacology; Breast Neoplasms - pathology; CAI; cytotoxicity; Drug Screening Assays, Antitumor - methods; Fluoresceins; Fluorescent Dyes; Humans; migration; Neoplasm Metastasis - prevention & control; Propidium; screening; Spectrometry, Fluorescence; tamoxifen; Tamoxifen - pharmacology; Triazoles - pharmacology; Tumor Cells, Cultured; migration; screening; CAI; cytotoxicity; tamoxifen
• ISSN: 0003-2697; 1096-0309
• DOI: 10.1006/abio.2000.4510

Large-scale screening strategies aimed at finding anticancer drugs traditionally focus on identifying cytotoxic compounds that attack actively dividing cells. Because progression to malignancy involves acquisition of an aggressively invasive phenotype in addition to hyperproliferation, simple and effective screening strategies for finding compounds that target the invasive aspects of cancer progression may prove valuable for identifying alternative and preventative cancer therapies. Here, we describe a fluorescence-based automated assay for identifying antimigratory compounds, with the ability to discern cytotoxic from noncytotoxic modes of action. With this assay, we analyzed the effects of two drugs on tumorigenic (MDA-MB-435) and nontumorigenic (MCF-10A) human breast cell lines. We chose to compare carboxyamido-triazole (CAI), an experimental compound shown to inhibit migration of various cell types, with tamoxifen, a common preventative and therapeutic anticancer compound. Our assay demonstrated that both these compounds inhibit migration at sublethal concentrations. Furthermore, CAI was more effective than tamoxifen at inhibiting chemotactic and haptotactic migration of both cell lines at all concentrations tested.