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 Lindholm, P. Articles by Backlund, A. Search for Related Content PubMed PubMed Citation Articles by Lindholm, P. Articles by Backlund, A.

Division of Pharmacognosy, Department of Medicinal Chemistry, BMC, Uppsala University, S-751 23 [P. L., U. G., S. J., P. C., L. B., A. B.], and Division of Clinical Pharmacology, Department of Medical Sciences, University Hospital, Uppsala University, S-751 85 [J. G., R. L.] Uppsala, Sweden

Cytotoxic activities of three naturally occurring macrocyclic peptides (cyclotides) isolated from the two violets, Viola arvensis Murr. and Viola odorata L., were investigated. A nonclonogenic fluorometric microculture assay was used to examine cytotoxicity in a panel of 10 human tumor cell lines representing defined types of cytotoxic drug resistance. Additionally, primary cultures of tumor cells from patients, and for comparison normal lymphocytes, were used to quantify cytotoxic activity. All three cyclotides, varv A, varv F, and cycloviolacin O2, exhibited strong cytotoxic activities, which varied in a dose-dependent manner. Cycloviolacin O2 was the most potent in all cell lines (IC₅₀ 0.1–0.3 µM), followed by varv A (IC₅₀ 2.7–6.35 µM) and varv F (IC₅₀ 2.6–7.4 µM), respectively. Activity profiles of the cyclotides differed significantly from those of antitumor drugs in clinical use, which may indicate a new mode of action. This, together with the exceptional chemical and biological stability of cyclotides, makes them interesting in particular for their potential as pharmacological tools and possibly as leads to antitumor agents.

This article has been cited by other articles:

				C. W. Gruber, A. G. Elliott, D. C. Ireland, P. G. Delprete, S. Dessein, U. Goransson, M. Trabi, C. K. Wang, A. B. Kinghorn, E. Robbrecht, et al. Distribution and Evolution of Circular Miniproteins in Flowering Plants PLANT CELL, September 1, 2008; 20(9): 2471 - 2483. [Abstract] [Full Text] [PDF]

				S. M. Simonsen, L. Sando, K. J. Rosengren, C. K. Wang, M. L. Colgrave, N. L. Daly, and D. J. Craik Alanine Scanning Mutagenesis of the Prototypic Cyclotide Reveals a Cluster of Residues Essential for Bioactivity J. Biol. Chem., April 11, 2008; 283(15): 9805 - 9813. [Abstract] [Full Text] [PDF]

				I. Saska, A. D. Gillon, N. Hatsugai, R. G. Dietzgen, I. Hara-Nishimura, M. A. Anderson, and D. J. Craik An Asparaginyl Endopeptidase Mediates in Vivo Protein Backbone Cyclization J. Biol. Chem., October 5, 2007; 282(40): 29721 - 29728. [Abstract] [Full Text] [PDF]

				J. P. Mulvenna, J. S. Mylne, R. Bharathi, R. A. Burton, N. J. Shirley, G. B. Fincher, M. A. Anderson, and D. J. Craik Discovery of Cyclotide-Like Protein Sequences in Graminaceous Crop Plants: Ancestral Precursors of Circular Proteins? PLANT CELL, September 1, 2006; 18(9): 2134 - 2144. [Abstract] [Full Text] [PDF]

				B. Chen, M. L. Colgrave, N. L. Daly, K. J. Rosengren, K. R. Gustafson, and D. J. Craik Isolation and Characterization of Novel Cyclotides from Viola hederaceae: SOLUTION STRUCTURE AND ANTI-HIV ACTIVITY OF vhl-1, A LEAF-SPECIFIC EXPRESSED CYCLOTIDE J. Biol. Chem., June 10, 2005; 280(23): 22395 - 22405. [Abstract] [Full Text] [PDF]

				F. Hillger, G. Herr, R. Rudolph, and E. Schwarz Biophysical Comparison of BMP-2, ProBMP-2, and the Free Pro-peptide Reveals Stabilization of the Pro-peptide by the Mature Growth Factor J. Biol. Chem., April 15, 2005; 280(15): 14974 - 14980. [Abstract] [Full Text] [PDF]

				M. Trabi and D. J. Craik Tissue-Specific Expression of Head-to-Tail Cyclized Miniproteins in Violaceae and Structure Determination of the Root Cyclotide Viola hederacea root cyclotide1 PLANT CELL, August 1, 2004; 16(8): 2204 - 2216. [Abstract] [Full Text] [PDF]

				A. Nourse, M. Trabi, N. L. Daly, and D. J. Craik A Comparison of the Self-association Behavior of the Plant Cyclotides Kalata B1 and Kalata B2 via Analytical Ultracentrifugation J. Biol. Chem., January 2, 2004; 279(1): 562 - 570. [Abstract] [Full Text] [PDF]

				U. Goransson and D. J. Craik Disulfide Mapping of the Cyclotide Kalata B1: CHEMICAL PROOF OF THE CYCLIC CYSTINE KNOT MOTIF J. Biol. Chem., November 28, 2003; 278(48): 48188 - 48196. [Abstract] [Full Text] [PDF]

				P. Lindholm, J. Gullbo, P. Claeson, U. Goransson, S. Johansson, A. Backlund, R. Larsson, and L. Bohlin Selective Cytotoxicity Evaluation in Anticancer Drug Screening of Fractionated Plant Extracts J Biomol Screen, August 1, 2002; 7(4): 333 - 340. [Abstract] [PDF]