title: Metabolic Effect of Estrogen Receptor Agonists on Breast Cancer Cells in the Presence or Absence of Carbonic Anhydrase Inhibitors.
abstract: Metabolic shift is one of the major hallmarks of cancer development. Estrogen receptor (ER) activity has a profound effect on breast cancer cell growth through a number of metabolic changes driven by its effect on transcription of several enzymes, including carbonic anhydrases, Stearoyl-CoA desaturase-1, and oncogenes including HER2. Thus, estrogen receptor activators can be expected to lead to the modulation of cell metabolism in estrogen receptor positive cells. In this work we have investigated the effect of 17β-estradiol, an ER activator, and ferulic acid, a carbonic anhydrase inhibitor, as well as ER activator, in the absence and in the presence of the carbonic anhydrase inhibitor acetazolamide on the metabolism of MCF7 cells and MCF7 cells, stably transfected to express HER2 (MCF7HER2). Metabolic profiles were studied using 1D and 2D metabolomic Nuclear Magnetic Resonance (NMR) experiments, combined with the identification and quantification of metabolites, and the annotation of the results in the context of biochemical pathways. Overall changes in hydrophilic metabolites were largest following treatment of MCF7 and MC7HER2 cells with 17β-estradiol. However, the carbonic anhydrase inhibitor acetazolamide had the largest effect on the profile of lipophilic metabolites.
authors.affiliation: Department of Chemistry and Biochemistry, Universit&#233; de Moncton, Moncton, NB E1A 3E9, Canada. Anissa.Belkaid@vitalitenb.ca.|Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada. Anissa.Belkaid@vitalitenb.ca.
authors.forename: Anissa
authors.initials: A
authors.lastname: Belkaid
authors.affiliation: National Research Council of Canada, 1200 Montreal Road, Ottawa, ON, Canada. cuperlovim@nrc.ca.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Čuperlović-Culf
authors.affiliation: Department of Chemistry and Biochemistry, Universit&#233; de Moncton, Moncton, NB E1A 3E9, Canada. mohamed.touaibia@umoncton.ca.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Touaibia
authors.affiliation: Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada. RodneyO@rrsb.nb.ca.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Ouellette
authors.affiliation: Department of Chemistry and Biochemistry, Universit&#233; de Moncton, Moncton, NB E1A 3E9, Canada. marc.surette@umoncton.ca.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Surette
keywords: 17β-estradiol; ER + cells; acetazolamide; cancer metabolism; carbonic anhydrase; ferulic acid; metabolomics