This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Roberge, M. Articles by Andersen, R. J. Search for Related Content PubMed PubMed Citation Articles by Roberge, M. Articles by Andersen, R. J.

Cell-based Screen for Antimitotic Agents and Identification of Analogues of Rhizoxin, Eleutherobin, and Paclitaxel in Natural Extracts¹

Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, V6T 1Z3 Canada [M. R., H. J. A., L. L., X. J., C. M. B.]; Departments of Chemistry and Oceanography (EOS), University of British Columbia, Vancouver, V6T 1Z1 Canada [B. C., L. X., R. J. A.]; and SeaTek Marine Biotechnology, Inc., Surrey, British Columbia, V4A 7M4 Canada [M. T. K.]

We describe a cell-based assay for antimitotic compounds that is suitable for drug discovery and for quantitative determination of antimitotic activity. In the assay, cells arrested in mitosis as a result of exposure to antimitotic agents in pure form or in crude natural extracts are detected by ELISA using the monoclonal antibody TG-3. The assay was used to screen >24,000 extracts of marine microorganisms and invertebrates and terrestrial plants and to guide the purification of active compounds from 5 of 119 positive extracts. A new rhizoxin analogue was found in a Pseudomonas species, six new eleutherobin analogues were identified from the octocoral Erythropodium caribaeorum, and two paclitaxel analogues were found in the stem bark of the tree Ilex macrophylla. The assay was also used for quantitative comparison of the antimitotic activity of different analogues. It revealed the importance of the C-11 to C-13 segment of the diterpene core of eleutherobin for its antimitotic activity. The identification of antimitotic compounds in very low abundance and their high (0.5%) occurrence in natural extracts indicates that drug discovery efforts using this cell-based assay may lead to the identification of structurally novel antimitotic agents.

This article has been cited by other articles:

				J. E. Loper, M. D. Henkels, B. T. Shaffer, F. A. Valeriote, and H. Gross Isolation and Identification of Rhizoxin Analogs from Pseudomonas fluorescens Pf-5 by Using a Genomic Mining Strategy Appl. Envir. Microbiol., May 15, 2008; 74(10): 3085 - 3093. [Abstract] [Full Text] [PDF]

				X. Fonrose, F. Ausseil, E. Soleilhac, V. Masson, B. David, I. Pouny, J.-C. Cintrat, B. Rousseau, C. Barette, G. Massiot, et al. Parthenolide Inhibits Tubulin Carboxypeptidase Activity Cancer Res., April 1, 2007; 67(7): 3371 - 3378. [Abstract] [Full Text] [PDF]

				E. Vassal, C. Barette, X. Fonrose, R. Dupont, E. Sans-Soleilhac, and L. Lafanechere Miniaturization and Validation of a Sensitive Multiparametric Cell-Based Assay for the Concomitant Detection of Microtubule-Destabilizing and Microtubule-Stabilizing Agents J Biomol Screen, June 1, 2006; 11(4): 377 - 389. [Abstract] [PDF]

				D. Sampath, L. M. Greenberger, C. Beyer, M. Hari, H. Liu, M. Baxter, S. Yang, C. Rios, and C. Discafani Preclinical Pharmacologic Evaluation of MST-997, an Orally Active Taxane with Superior In vitro and In vivo Efficacy in Paclitaxel- and Docetaxel-Resistant Tumor Models. Clin. Cancer Res., June 1, 2006; 12(11): 3459 - 3469. [Abstract] [Full Text] [PDF]

				X. Jiang, B. Zhao, R. Britton, L. Y. Lim, D. Leong, J. S. Sanghera, B.-B. S. Zhou, E. Piers, R. J. Andersen, and M. Roberge Inhibition of Chk1 by the G2 DNA damage checkpoint inhibitor isogranulatimide Mol. Cancer Ther., October 1, 2004; 3(10): 1221 - 1227. [Abstract] [Full Text] [PDF]

				S. DeBonis, D. A. Skoufias, L. Lebeau, R. Lopez, G. Robin, R. L. Margolis, R. H. Wade, and F. Kozielski In vitro screening for inhibitors of the human mitotic kinesin Eg5 with antimitotic and antitumor activities Mol. Cancer Ther., September 1, 2004; 3(9): 1079 - 1090. [Abstract] [Full Text] [PDF]