Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell
Lines: Associations With Cancer Progression

J 2017

Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression

KRATOCHVÍLOVÁ, Monika, Martina RAUDENSKÁ, Zbynek HEGER, Lukas RICHTERA, Natalia CERNEI et. al.

Basic information

Original name

Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression

Authors

KRATOCHVÍLOVÁ, Monika (203 Czech Republic, belonging to the institution), Martina RAUDENSKÁ (203 Czech Republic, belonging to the institution), Zbynek HEGER (203 Czech Republic), Lukas RICHTERA (203 Czech Republic), Natalia CERNEI (203 Czech Republic), Vojtech ADAM (203 Czech Republic), Petr BABULA (203 Czech Republic, belonging to the institution), Marie NOVÁKOVÁ (203 Czech Republic, belonging to the institution), Michal MASAŘÍK (203 Czech Republic, guarantor, belonging to the institution) and Jaromír GUMULEC (203 Czech Republic, belonging to the institution)

Edition

Prostate, Hoboken, Wiley-Blackwell, 2017, 0270-4137

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30202 Endocrinology and metabolism

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.347

RIV identification code

RIV/00216224:14110/17:00096422

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1002/pros.23304

UT WoS

000397496300005

Keywords in English

amino acid; aspartate; metabolomics; resistance; zinc

Abstract

V originále

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.

Links

MUNI/A/1365/2015, interní kód MU

Name: Kardiovaskulární systém: od modelu přes terapii k prevenci (Acronym: KAMOTEPRE)

Investor: Masaryk University, Category A

ROZV/20/LF/2015, interní kód MU

Name: LF - Příspěvek IP 2015

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

KRATOCHVÍLOVÁ, Monika, Martina RAUDENSKÁ, Zbynek HEGER, Lukas RICHTERA, Natalia CERNEI, Vojtech ADAM, Petr BABULA, Marie NOVÁKOVÁ, Michal MASAŘÍK and Jaromír GUMULEC. Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression. Prostate. Hoboken: Wiley-Blackwell, 2017, vol. 77, No 6, p. 604-616. ISSN 0270-4137. Available from: https://dx.doi.org/10.1002/pros.23304.

@article{1377538,
   author = {Kratochvílová, Monika and Raudenská, Martina and Heger, Zbynek and Richtera, Lukas and Cernei, Natalia and Adam, Vojtech and Babula, Petr and Nováková, Marie and Masařík, Michal and Gumulec, Jaromír},
   article_location = {Hoboken},
   article_number = {6},
   doi = {http://dx.doi.org/10.1002/pros.23304},
   keywords = {amino acid; aspartate; metabolomics; resistance; zinc},
   language = {eng},
   issn = {0270-4137},
   journal = {Prostate},
   title = {Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression},
   volume = {77},
   year = {2017}
}

TY  - JOUR
ID  - 1377538
AU  - Kratochvílová, Monika - Raudenská, Martina - Heger, Zbynek - Richtera, Lukas - Cernei, Natalia - Adam, Vojtech - Babula, Petr - Nováková, Marie - Masařík, Michal - Gumulec, Jaromír
PY  - 2017
TI  - Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression
JF  - Prostate
VL  - 77
IS  - 6
SP  - 604-616
EP  - 604-616
PB  - Wiley-Blackwell
SN  - 02704137
KW  - amino acid
KW  - aspartate
KW  - metabolomics
KW  - resistance
KW  - zinc
N2  - 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.
ER  -

KRATOCHVÍLOVÁ, Monika, Martina RAUDENSKÁ, Zbynek HEGER, Lukas RICHTERA, Natalia CERNEI, Vojtech ADAM, Petr BABULA, Marie NOVÁKOVÁ, Michal MASAŘÍK and Jaromír GUMULEC. Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression. \textit{Prostate}. Hoboken: Wiley-Blackwell, 2017, vol.~77, No~6, p.~604-616. ISSN~0270-4137. Available from: https://dx.doi.org/10.1002/pros.23304.

Detailed Information on Publication Record