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Evaluation of toxicity and anti-tumour activity of cycloviolacin O2 in mice.
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- Burman, Robert, 1979- (author)
- Uppsala universitet,Avdelningen för farmakognosi
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- Svedlund, Erika (author)
- Uppsala universitet,Avdelningen för farmakognosi
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- Felth, Jenny, 1979- (author)
- Uppsala universitet,Avdelningen för farmakognosi
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- (creator_code:org_t)
- 2010-05-26
- 2010
- English.
- In: Biopolymers. - : Wiley. - 0006-3525 .- 1097-0282. ; 94:5, s. 626-634
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- Cyclotides
- toxicity
- in vivo
- xenograft
- cycloviolacin O2
- PHARMACY
- FARMACI
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- art (subject category)
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- Biopolymers
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- Uppsala University
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