Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
28101932
DOI
10.1002/pros.23304
Knihovny.cz E-resources
- Keywords
- amino acid, aspartate, metabolomics, resistance, zinc,
- MeSH
- Amino Acids genetics MeSH
- Drug Resistance, Neoplasm drug effects genetics MeSH
- Adult MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Prostatic Neoplasms drug therapy genetics pathology MeSH
- Cell Movement drug effects physiology MeSH
- Disease Progression * MeSH
- Gene Expression Profiling methods MeSH
- Zinc pharmacology therapeutic use MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Amino Acids MeSH
- Zinc 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
References provided by Crossref.org
Long-term zinc treatment alters the mechanical properties and metabolism of prostate cancer cells
