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

Int J Mol Sci. 2016 Oct 24;17(10):1772. doi: 10.3390/ijms17101772.


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.

Keywords: 4-acyl pyrrole derivative; BRD-related tumors; GC-MS; Michigan Cancer Foundation-7 (MCF-7); XD14; cancer therapy; metabolic profiling.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Breast / drug effects
  • Breast / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Discriminant Analysis
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Least-Squares Analysis
  • MCF-7 Cells
  • Metabolic Networks and Pathways / drug effects
  • Metabolome / drug effects*
  • Metabolomics
  • Principal Component Analysis
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*


  • Antineoplastic Agents
  • Pyrroles