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

Authors :
Pan, Daqiang
Kather, Michel
Willmann, Lucas
Schlimpert, Manuel
Bauer, Christoph
Lagies, Simon
Schmidtkunz, Karin
Eisenhardt, Steffen U.
Jung, Manfred
Günther, Stefan
Kammerer, Bernd
Source :
International Journal of Molecular Sciences; Oct2016, Vol. 17 Issue 10, p1772, 15p, 1 Diagram, 4 Charts, 8 Graphs
Publication Year :
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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16616596
Volume :
17
Issue :
10
Database :
Complementary Index
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
119112846
Full Text :
https://doi.org/10.3390/ijms17101772