Cisplatin-resistant prostate cancer model: Differences in
antioxidant system, apoptosis and cell cycle

J 2014

Cisplatin-resistant prostate cancer model: Differences in antioxidant system, apoptosis and cell cycle

GUMULEC, Jaromír, Jan BALVAN, Markéta SZTALMACHOVÁ, Martina RAUDENSKÁ, Veronika DVOŘÁKOVÁ et. al.

Basic information

Original name

Cisplatin-resistant prostate cancer model: Differences in antioxidant system, apoptosis and cell cycle

Authors

GUMULEC, Jaromír (203 Czech Republic, belonging to the institution), Jan BALVAN (203 Czech Republic, belonging to the institution), Markéta SZTALMACHOVÁ (203 Czech Republic, belonging to the institution), Martina RAUDENSKÁ (203 Czech Republic, belonging to the institution), Veronika DVOŘÁKOVÁ (203 Czech Republic, belonging to the institution), Lucia KNOPFOVÁ (203 Czech Republic, belonging to the institution), Hana POLANSKÁ (203 Czech Republic, belonging to the institution), Kristýna HUDCOVÁ (203 Czech Republic, belonging to the institution), Branislav RUTTKAY-NEDECKÝ (203 Czech Republic), Petr BABULA (203 Czech Republic), Vojtěch ADAM (203 Czech Republic), René KIZEK (203 Czech Republic), Marie STIBOROVÁ (203 Czech Republic) and Michal MASAŘÍK (203 Czech Republic, guarantor, belonging to the institution)

Edition

International Journal of Oncology, University of Crete, Faculty of Medicine, Laboratory of Clinical Virology, 2014, 1019-6439

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

Greece

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.025

RIV identification code

RIV/00216224:14110/14:00075570

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3892/ijo.2013.2223

UT WoS

000336894900034

Keywords in English

Cell cycle; Cisplatin; Oxidative stress; Prostate cancer; Resistance

Abstract

V originále

Differences in the antioxidant system, apoptotic mechanism and in cell cycle between prostatic cell lines could partially elucidate the development of cisplatin resistance. The aim of this study was to identify the most characteristic parameter for a particular cell line and/or a particular cisplatin treatment using a general regression model and to assess whether it is possible to use measured parameters as markers of cisplatin resistance. This study integrates the results of viability, antioxidant, flow cytometric and quantitative PCR assays in order to characterize the resistance of prostate cancer to cisplatin. Cell growth using metabolic- (MTT) and impedance-based assays, the expression of key cell death signaling proteins (p53, Bax and Bcl-2), cell cycle, activity of antioxidant system-related proteins (superoxide dismutase, glutathione peroxidase, glutathione reductase and metallothionein) and free radical scavenging capacity assays [free radicals (FR), ferric reducing antioxidant power (FRAP), ABTS] were analyzed in the cell lines 22Rv1, PC-3 and PNT1A with respect to rising concentrations and different length of cisplatin treatment (12-72 h). The non-functional-p53 PC-3 cell line showed decreased BAX (p<0.05) and, in contrast to PNT1A and 22Rv1, no cisplatin-induced effects on cell cycle. All cell lines showed increasing levels of free radical scavenging activity by ABTS, FRAP and FR assays in a time- and dose-dependent manner (r>0.76 at p<0.001 for ABTS, FRAP and FR at p<0.001). PC-3 showed increased (p<0.05) levels of free radical scavenging activity by ABTS and FR methods. These findings, together with significantly elevated MT, decreased p53 and Bax indicate PC-3 to be cisplatin-resistant. The differences in the antioxidant system and apoptotic mechanisms in PC-3 cells may elucidate the development of cisplatin resistance and indicate that this cell line may be further studied as a model of cytostatic resistance.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

EE2.3.20.0183, research and development project

Name: Centrum experimentální biomedicíny

Citovat

GUMULEC, Jaromír, Jan BALVAN, Markéta SZTALMACHOVÁ, Martina RAUDENSKÁ, Veronika DVOŘÁKOVÁ, Lucia KNOPFOVÁ, Hana POLANSKÁ, Kristýna HUDCOVÁ, Branislav RUTTKAY-NEDECKÝ, Petr BABULA, Vojtěch ADAM, René KIZEK, Marie STIBOROVÁ and Michal MASAŘÍK. Cisplatin-resistant prostate cancer model: Differences in antioxidant system, apoptosis and cell cycle. International Journal of Oncology. University of Crete, Faculty of Medicine, Laboratory of Clinical Virology, 2014, vol. 44, No 3, p. 923-933. ISSN 1019-6439. Available from: https://dx.doi.org/10.3892/ijo.2013.2223.

@article{1183879,
   author = {Gumulec, Jaromír and Balvan, Jan and Sztalmachová, Markéta and Raudenská, Martina and Dvořáková, Veronika and Knopfová, Lucia and Polanská, Hana and Hudcová, Kristýna and RuttkayandNedecký, Branislav and Babula, Petr and Adam, Vojtěch and Kizek, René and Stiborová, Marie and Masařík, Michal},
   article_number = {3},
   doi = {http://dx.doi.org/10.3892/ijo.2013.2223},
   keywords = {Cell cycle; Cisplatin; Oxidative stress; Prostate cancer; Resistance},
   language = {eng},
   issn = {1019-6439},
   journal = {International Journal of Oncology},
   title = {Cisplatin-resistant prostate cancer model: Differences in antioxidant system, apoptosis and cell cycle},
   volume = {44},
   year = {2014}
}

TY  - JOUR
ID  - 1183879
AU  - Gumulec, Jaromír - Balvan, Jan - Sztalmachová, Markéta - Raudenská, Martina - Dvořáková, Veronika - Knopfová, Lucia - Polanská, Hana - Hudcová, Kristýna - Ruttkay-Nedecký, Branislav - Babula, Petr - Adam, Vojtěch - Kizek, René - Stiborová, Marie - Masařík, Michal
PY  - 2014
TI  - Cisplatin-resistant prostate cancer model: Differences in antioxidant system, apoptosis and cell cycle
JF  - International Journal of Oncology
VL  - 44
IS  - 3
SP  - 923-933
EP  - 923-933
PB  - University of Crete, Faculty of Medicine, Laboratory of Clinical Virology
SN  - 10196439
KW  - Cell cycle
KW  - Cisplatin
KW  - Oxidative stress
KW  - Prostate cancer
KW  - Resistance
N2  - Differences in the antioxidant system, apoptotic mechanism and in cell cycle between prostatic cell lines could partially elucidate the development of cisplatin resistance. The aim of this study was to identify the most characteristic parameter for a particular cell line and/or a particular cisplatin treatment using a general regression model and to assess whether it is possible to use measured parameters as markers of cisplatin resistance. This study integrates the results of viability, antioxidant, flow cytometric and quantitative PCR assays in order to characterize the resistance of prostate cancer to cisplatin. Cell growth using metabolic- (MTT) and impedance-based assays, the expression of key cell death signaling proteins (p53, Bax and Bcl-2), cell cycle, activity of antioxidant system-related proteins (superoxide dismutase, glutathione peroxidase, glutathione reductase and metallothionein) and free radical scavenging capacity assays [free radicals (FR), ferric reducing antioxidant power (FRAP), ABTS] were analyzed in the cell lines 22Rv1, PC-3 and PNT1A with respect to rising concentrations and different length of cisplatin treatment (12-72 h). The non-functional-p53 PC-3 cell line showed decreased BAX (p<0.05) and, in contrast to PNT1A and 22Rv1, no cisplatin-induced effects on cell cycle. All cell lines showed increasing levels of free radical scavenging activity by ABTS, FRAP and FR assays in a time- and dose-dependent manner (r>0.76 at p<0.001 for ABTS, FRAP and FR at p<0.001). PC-3 showed increased (p<0.05) levels of free radical scavenging activity by ABTS and FR methods. These findings, together with significantly elevated MT, decreased p53 and Bax indicate PC-3 to be cisplatin-resistant. The differences in the antioxidant system and apoptotic mechanisms in PC-3 cells may elucidate the development of cisplatin resistance and indicate that this cell line may be further studied as a model of cytostatic resistance.
ER  -

GUMULEC, Jaromír, Jan BALVAN, Markéta SZTALMACHOVÁ, Martina RAUDENSKÁ, Veronika DVOŘÁKOVÁ, Lucia KNOPFOVÁ, Hana POLANSKÁ, Kristýna HUDCOVÁ, Branislav RUTTKAY-NEDECKÝ, Petr BABULA, Vojtěch ADAM, René KIZEK, Marie STIBOROVÁ and Michal MASAŘÍK. Cisplatin-resistant prostate cancer model: Differences in antioxidant system, apoptosis and cell cycle. \textit{International Journal of Oncology}. University of Crete, Faculty of Medicine, Laboratory of Clinical Virology, 2014, vol.~44, No~3, p.~923-933. ISSN~1019-6439. Available from: https://dx.doi.org/10.3892/ijo.2013.2223.

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