Cisplatin-resistant prostate cancer model: Differences in antioxidant system, apoptosis and cell cycle
Language English Country Greece Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24366574
DOI
10.3892/ijo.2013.2223
Knihovny.cz E-resources
- MeSH
- Antioxidants metabolism MeSH
- Apoptosis drug effects MeSH
- Cell Cycle drug effects genetics MeSH
- Drug Resistance, Neoplasm genetics MeSH
- Cisplatin therapeutic use MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Tumor Suppressor Protein p53 genetics MeSH
- Prostatic Neoplasms drug therapy genetics pathology MeSH
- Cell Proliferation drug effects MeSH
- Signal Transduction genetics MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antioxidants MeSH
- Cisplatin MeSH
- Tumor Suppressor Protein p53 MeSH
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 (0-150 µM) 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.
Department of Biochemistry Faculty of Science Charles University CZ 128 40 Prague 2 Czech Republic
Department of Chemistry and Biochemistry Mendel University in Brno CZ 613 00 Brno Czech Republic
References provided by Crossref.org
Long-term zinc treatment alters the mechanical properties and metabolism of prostate cancer cells
Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma
The Quantitative-Phase Dynamics of Apoptosis and Lytic Cell Death
Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating
Multimodal holographic microscopy: distinction between apoptosis and oncosis
