Quaternary ammonium-melphalan conjugate for anticancer therapy of chondrosarcoma: in vitro and in vivo preclinical studies View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2012-08

AUTHORS

Caroline Peyrode, Valérie Weber, Emmanuelle David, Aurélien Vidal, Philippe Auzeloux, Yves Communal, Marie Mélanie Dauplat, Sophie Besse, François Gouin, Dominique Heymann, Jean Michel Chezal, François Rédini, Elisabeth Miot-Noirault

ABSTRACT

Cartilage tumours present ongoing therapeutic challenges due to their chondrogenic extracellular matrix that potentially hampers drug delivery, their low percentage of dividing cells, and their poor vascularity. In this context, and based on the affinity of the quaternary ammonium moiety for proteoglycans (PG), we developed a strategy that uses the quaternary ammonium function to selectively deliver DNA alkylating agents to the cartilage tumour tissue. We engineered the quaternary ammonium derivative of melphalan (Mel-AQ) and assessed its antitumoural activity in vitro and in vivo. In vitro, micromolar concentrations of Mel-AQ inhibited the proliferation of human HEMC-SS chondrosarcoma and Saos-2 osteosarcoma cell lines. Moreover, 24-h incubation with 20 μM Mel-AQ induced a 2.5-fold increase in S population and a 1.5-fold increase in subG0G1 population compared to controls. In vivo, Mel-AQ demonstrated antitumour activity in the orthotopic model of primary Swarm rat chondrosarcoma. When given to chondrosarcoma-bearing rats (three doses of 16 μmol/kg at days 8, 12 and 16 post-implant), Mel-AQ demonstrated an optimal antitumour effect at day 43, when tumour cell growth inhibition peaked at 69%. Interestingly, the treatment protocol was proved well tolerated, since the animals showed no weight loss over the course of the study. This antitumoural effect was assessed in vivo by scintigraphic imaging using (99m)Tc-NTP 15-5 developed in our lab as a PG-targeting radiotracer, and tumour tissue was analyzed at study-end by biochemical PG assay with Alcian blue staining. Mel-AQ treatment led to a significant decrease in the PG content of tumoural tissue. These experimental results highlighted the promising antitumour potential of Mel-AQ as a PG-targeting strategy for therapeutic management of chondrosarcoma. More... »

PAGES

1782-1790

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10637-011-9663-z

DOI

http://dx.doi.org/10.1007/s10637-011-9663-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028393554

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21499733


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s10637-011-9663-z'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s10637-011-9663-z'

Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s10637-011-9663-z'


 

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