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Int. J. Mol. Sci. 2016, 17(10), 1772; doi:10.3390/ijms17101772

Metabolic Response to XD14 Treatment in Human Breast Cancer Cell Line MCF-7

1
Center for Biological Systems Analysis ZBSA, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany
2
Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany
3
Institute of Biology II, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany
4
Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany
5
Department of Plastic and Hand Surgery, University of Freiburg Medical Center, 79106 Freiburg, Germany
6
BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Ting-Li (Morgan) Han, Philip Newton Baker and Elizabeth McKenzie
Received: 7 July 2016 / Revised: 4 October 2016 / Accepted: 17 October 2016 / Published: 24 October 2016
(This article belongs to the Special Issue Metabolomic Technologies in Medicine)
View Full-Text   |   Download PDF [5595 KB, uploaded 24 October 2016]   |  

Abstract

XD14 is a 4-acyl pyrrole derivative, which was discovered by a high-throughput virtual screening experiment. XD14 inhibits bromodomain and extra-terminal domain (BET) proteins (BRD2, BRD3, BRD4 and BRDT) and consequently suppresses cell proliferation. In this study, metabolic profiling reveals the molecular effects in the human breast cancer cell line MCF-7 (Michigan Cancer Foundation-7) treated by XD14. A three-day time series experiment with two concentrations of XD14 was performed. Gas chromatography-mass spectrometry (GC-MS) was applied for untargeted profiling of treated and non-treated MCF-7 cells. The gained data sets were evaluated by several statistical methods: analysis of variance (ANOVA), clustering analysis, principle component analysis (PCA), and partial least squares discriminant analysis (PLS-DA). Cell proliferation was strongly inhibited by treatment with 50 µM XD14. Samples could be discriminated by time and XD14 concentration using PLS-DA. From the 117 identified metabolites, 67 were significantly altered after XD14 treatment. These metabolites include amino acids, fatty acids, Krebs cycle and glycolysis intermediates, as well as compounds of purine and pyrimidine metabolism. This massive intervention in energy metabolism and the lack of available nucleotides could explain the decreased proliferation rate of the cancer cells. View Full-Text
Keywords: XD14; 4-acyl pyrrole derivative; Michigan Cancer Foundation-7 (MCF-7); GC-MS; metabolic profiling; cancer therapy; BRD-related tumors XD14; 4-acyl pyrrole derivative; Michigan Cancer Foundation-7 (MCF-7); GC-MS; metabolic profiling; cancer therapy; BRD-related tumors
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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. (CC BY 4.0).

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MDPI and ACS Style

Pan, D.; Kather, M.; Willmann, L.; Schlimpert, M.; Bauer, C.; Lagies, S.; Schmidtkunz, K.; Eisenhardt, S.U.; Jung, M.; Günther, S.; Kammerer, B. Metabolic Response to XD14 Treatment in Human Breast Cancer Cell Line MCF-7. Int. J. Mol. Sci. 2016, 17, 1772.

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