Evaluation of toxicity and antitumor activity of cycloviolacin O2 in mice

Burman, Robert, Svedlund, Erika, Felth, Jenny, Hassan, Saadia, Hermann, Anders, Clark, Richard James, Craik, David J., Bohlin, Lars, Claeson, Per, Goransson, Ulf and Gullbo, Joachim (2010). Evaluation of toxicity and antitumor activity of cycloviolacin O2 in mice. In: Proceedings of the 1st International Conference on Circular Proteins. 1st International Conference on Circular Proteins, Heron Island, Qld, Australia, (626-634). 18-21 October, 2009. doi:10.1002/bip.21408

Author Burman, Robert
Svedlund, Erika
Felth, Jenny
Hassan, Saadia
Hermann, Anders
Clark, Richard James
Craik, David J.
Bohlin, Lars
Claeson, Per
Goransson, Ulf
Gullbo, Joachim
Title of paper Evaluation of toxicity and antitumor activity of cycloviolacin O2 in mice
Conference name 1st International Conference on Circular Proteins
Conference location Heron Island, Qld, Australia
Conference dates 18-21 October, 2009
Proceedings title Proceedings of the 1st International Conference on Circular Proteins   Check publisher's open access policy
Journal name Peptide Science   Check publisher's open access policy
Place of Publication Hoboken, NJ, U.S.A
Publisher Wiley Interscience
Publication Year 2010
Year available 2010
Sub-type Fully published paper
DOI 10.1002/bip.21408
Open Access Status Not Open Access
ISSN 0006-3525
Volume 94
Issue 5
Start page 626
End page 634
Total pages 9
Language eng
Formatted Abstract/Summary
Cycloviolacin O2 is a small cyclic cysteine-rich protein belonging to the group of plant proteins called cyclotides. This cyclotide has been previously shown to exert cytotoxic activity against a variety of human tumor cell lines as well as primary cultures of human tumor cells in vitro. This study is the first evaluation of its tolerability and antitumor activity in vivo. Maximal-tolerated doses were estimated to 1.5 mg/kg for single intravenous (i.v.) dosing and 0.5 mg/kg for daily repeated dosing, respectively. Two different in vivo methods were used: the hollow fiber method with single dosing (i.v. 1.0 mg/kg) and traditional xenografts with repeated dosing over 2 weeks (i.v. 0.5 mg/kg daily, 5 days a week). The human tumor cell lines used displayed dose-dependent in vitro sensitivity (including growth in hollow fibers to confirm passage of cycloviolacin O2 through the polyvinylidene fluoride fibers), with IC50 values in the micromolar range. Despite this sensitivity in vitro, no significant antitumor effects were detected in vivo, neither with single dosing in the hollow fiber method nor with repeated dosing in xenografts. In summary, the results indicate that antitumor effects are minor or absent at tolerable (sublethal) doses, and cycloviolacin O2 has a very abrupt in vivo toxicity profile, with lethality after single injection at 2 mg/kg, but no signs of discomfort to the animals at 1.5 mg/kg. Repeated dosing of 1 mg/kg gave a local-inflammatory reaction at the site of injection after 2–3 days; lower doses were without complications. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 626–634, 2010.
Keyword Cyclotides
Cycloviolacin O2
In vivo
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Peptide Science, Special Issue: Special Issue on International Conference on Circular Proteins, Article first published online: 4 August, 2010.

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Created: Wed, 02 Feb 2011, 01:04:03 EST by Susan Allen on behalf of Institute for Molecular Bioscience