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)]

1 Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand 2 Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology Lausanne (EPFL), CH-1015 Lausanne, Switzerland
* Author to whom correspondence should be addressed.
Received: 15 June 2012; in revised form: 25 August 2012 / Accepted: 8 October 2012 / Published: 15 October 2012
(This article belongs to the Special Issue Advances in Molecular Oncology)
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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

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MDPI and ACS Style

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.

AMA Style

Chakree K, Ovatlarnporn C, Dyson PJ, 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)]. International Journal of Molecular Sciences. 2012; 13(10):13183-13202.

Chicago/Turabian Style

Chakree, Korawan; Ovatlarnporn, Chitchamai; Dyson, Paul J.; Ratanaphan, Adisorn. 2012. "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. 13, no. 10: 13183-13202.

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