Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
28101932
DOI
10.1002/pros.23304
Knihovny.cz E-zdroje
- Klíčová slova
- amino acid, aspartate, metabolomics, resistance, zinc,
- MeSH
- aminokyseliny genetika MeSH
- chemorezistence účinky léků genetika MeSH
- dospělí MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prostaty farmakoterapie genetika patologie MeSH
- pohyb buněk účinky léků fyziologie MeSH
- progrese nemoci * MeSH
- stanovení celkové genové exprese metody MeSH
- zinek farmakologie terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aminokyseliny MeSH
- zinek MeSH
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. RESULTS AND 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.
Central European Institute of Technology Brno University of Technology Brno Czech Republic
Department of Chemistry and Biochemistry Mendel University in Brno Brno Czech Republic
Faculty of Medicine Department of Pathological Physiology Masaryk University Brno Czech Republic
Faculty of Medicine Department of Physiology Masaryk University Brno Czech Republic
Citace poskytuje Crossref.org
Long-term zinc treatment alters the mechanical properties and metabolism of prostate cancer cells
