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Issue 12, 2014
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In vivo anti-tumor activity of the organometallic ruthenium(ii)-arene complex [Ru(η6-p-cymene)Cl2(pta)] (RAPTA-C) in human ovarian and colorectal carcinomas

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Abstract

Based on the clinical success of platinum-based anti-cancer drugs such as cisplatin, carboplatin and oxaliplatin, a variety of other metal-based anti-cancer compounds are being investigated. In particular, a number of ruthenium-based compounds have been identified which exhibit unique biochemical properties and reduced toxicity profiles compared to the clinically used platinum-based drugs. We have developed a series of organometallic ruthenium(II)-arene complexes that were shown to exert anti-metastatic activity with relatively minor activity on primary tumor growth. Here, we show that the prototype compound, [Ru(η6-p-cymene)Cl2(pta)], where pta = 1,3,5-triaza-7-phosphaadamantane (RAPTA-C), reduces the growth of primary tumors in preclinical models for ovarian and colorectal carcinomas. When administered daily at relatively low doses (0.2 mg kg−1), RAPTA-C was shown to significantly reduce the growth of the A2780 ovarian carcinoma transplanted onto the chicken chorioallantoic membrane model. Similar activity was observed in LS174T colorectal carcinoma in athymic mice, albeit at a higher dose. In both models, a clear inhibition of microvessel density was observed, confirming the previously discovered anti-angiogenic mechanism of RAPTA-C. Biodistribution studies with radiolabeled (103Ru) RAPTA-C indicate that the compound is rapidly cleared from the organs and the bloodstream through excretion by the kidneys. As such, RAPTA-C is a promising compound for translation to clinical evaluation.

Graphical abstract: In vivo anti-tumor activity of the organometallic ruthenium(ii)-arene complex [Ru(η6-p-cymene)Cl2(pta)] (RAPTA-C) in human ovarian and colorectal carcinomas

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Supplementary files

Article information


Submitted
01 May 2014
Accepted
01 Aug 2014
First published
05 Aug 2014

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2014,5, 4742-4748
Article type
Edge Article
Author version available

In vivo anti-tumor activity of the organometallic ruthenium(II)-arene complex [Ru(η6-p-cymene)Cl2(pta)] (RAPTA-C) in human ovarian and colorectal carcinomas

A. Weiss, R. H. Berndsen, M. Dubois, C. Müller, R. Schibli, A. W. Griffioen, P. J. Dyson and P. Nowak-Sliwinska, Chem. Sci., 2014, 5, 4742
DOI: 10.1039/C4SC01255K

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