title: Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression.
abstract: BACKGROUND
  Failure in intracellular zinc accumulation is a key process in prostate carcinogenesis. Nevertheless, epidemiological studies of zinc administration have provided contradicting results. In order to examine the impact of the artificial intracellular increase of zinc(II) ions on prostate cancer metabolism, PNT1A, 22Rv1, and PC-3 prostatic cell lines-depicting different stages of cancer progression-and their zinc-resistant counterparts were used. To determine "benign" and "malignant" metabolic profiles, amino acid patterns, gene expression, and antioxidant capacity of these cell lines were assessed.
  
  
  METHODS
  Amino acid profiles were examined using an ion-exchange liquid chromatography. Intracellular zinc content was measured by atomic absorption spectrometry. Metallothionein was quantified using differential pulse voltammetry. The content of reduced glutathione was determined using high performance liquid chromatography coupled with an electrochemical detector. Cellular antioxidant capacity was determined by the ABTS test and gene expression analysis was performed by qRT-PCR.
  
  
  CONCLUSIONS
  Long-term zinc treatment was shown to reroute cell metabolism from benign to more malignant type. Long-term application of high concentration of zinc(II) significantly enhanced cisplatin resistance, invasiveness, cellular antioxidant capacity, synthesis of glutathione, and expression of treatment resistance- and stemness-associated genes (SOX2, POU5F1, BIRC5). Tumorous cell lines universally displayed high accumulation of aspartate and sarcosine and depletion of essential amino acids. Increased aspartate/threonine, aspartate/methionine, and sarcosine/serine ratios were associated with cancer phenotype with high levels of sensitivity and specificity. Prostate 77: 604-616, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Faculty of Medicine, Department of Physiology, Masaryk University, Brno, Czech Republic.|Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Kratochvilova
authors.affiliation: Faculty of Medicine, Department of Physiology, Masaryk University, Brno, Czech Republic.|Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Raudenska
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.|Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Heger
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.|Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic.
authors.forename: Lukas
authors.initials: L
authors.lastname: Richtera
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.|Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic.
authors.forename: Natalia
authors.initials: N
authors.lastname: Cernei
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.|Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Adam
authors.affiliation: Faculty of Medicine, Department of Physiology, Masaryk University, Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Babula
authors.affiliation: Faculty of Medicine, Department of Physiology, Masaryk University, Brno, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Novakova
authors.affiliation: Faculty of Medicine, Department of Physiology, Masaryk University, Brno, Czech Republic.|Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.|Faculty of Medicine, Department of Pathological Physiology, Masaryk University, Brno, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Masarik
authors.affiliation: Faculty of Medicine, Department of Physiology, Masaryk University, Brno, Czech Republic.|Faculty of Medicine, Department of Pathological Physiology, Masaryk University, Brno, Czech Republic.
authors.forename: Jaromir
authors.initials: J
authors.lastname: Gumulec
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015032:Zinc / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000596:Amino Acids; D015032:Zinc
keywords: amino acid; aspartate; metabolomics; resistance; zinc