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Int. J. Mol. Sci. 2012, 13(10), 13183-13202; doi:10.3390/ijms131013183
Article

Altered DNA Binding and Amplification of Human Breast Cancer Suppressor Gene BRCA1 Induced by a Novel Antitumor Compound, [Ru(η6-p-phenylethacrynate)Cl2(pta)]

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Received: 15 June 2012 / Revised: 25 August 2012 / Accepted: 8 October 2012 / Published: 15 October 2012
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
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Abstract

The ruthenium-based complex [Ru(η6-p-phenylethacrynate)Cl2(pta)] (pta = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane), termed ethaRAPTA, is an interesting antitumor compound. The elucidation of the molecular mechanism of drug activity is central to the drug development program. To this end, we have characterized the ethaRAPTA interaction with DNA, including probing the sequence specific modified DNA structural stability and DNA amplification using the breast cancer suppressor gene 1 (BRCA1) of human breast and colon adenocarcinoma cell lines as models. The preference of ethaRAPTA base binding is in the order A > G > T > C. Once modified, the ethaRAPTA-induced BRCA1 structure has higher thermal stability than the modified equivalents of its related compound, RAPTA-C. EthaRAPTA exhibits a higher efficiency than RAPTA-C in inhibiting BRCA1 amplification. With respect to both compounds, the inhibition of BRCA1 amplification is more effective in an isolated system than in cell lines. These data provide evidence that will help to understand the process of elucidating the pathways involved in the response induced by ethaRAPTA.
Keywords: BRCA1; DNA adducts; DNA amplification; ethaRAPTA; tumor suppressor gene BRCA1; DNA adducts; DNA amplification; ethaRAPTA; tumor suppressor gene
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Chakree, K.; Ovatlarnporn, C.; Dyson, P.J.; Ratanaphan, A. Altered DNA Binding and Amplification of Human Breast Cancer Suppressor Gene BRCA1 Induced by a Novel Antitumor Compound, [Ru(η6-p-phenylethacrynate)Cl2(pta)]. Int. J. Mol. Sci. 2012, 13, 13183-13202.

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