| Title |
Targeting prostate cancer cell metabolism: impact of hexokinase and CPT-1 enzymes
|
|---|---|
| Published in |
Tumor Biology, December 2014
|
| DOI | 10.1007/s13277-014-2919-4 |
| Pubmed ID | |
| Authors |
Rouhallah Najjar Sadeghi, Fatemeh Karami-Tehrani, Siamak Salami |
| Abstract |
Glycolysis has been shown to be required for the cell growth and proliferation in several cancer cells. However, prostate cancer cells were accused of using more fatty acid than glucose to meet their bioenergetic demands. The present study was designed to evaluate the involvement of hexokinase and CPT-1 in the cell growth and proliferation of human prostate cancer cell lines, PC3, and LNCaP-FGC-10. Hexokinase and CPT-1 activities were examined in the presence of different concentrations of their inhibitors, lonidamine and etomoxir, to find the concentration of maximum inhibition ([I max]). To assess cell viability and proliferation, dimethylthiazol (MTT) assay was carried out using [I max] for 24, 48, and 72 h on PC3 and LNCaP cells. Apoptosis was determined using annexin-V, caspase-3 activity assay, Hoechst 33258 staining, and evaluation of mitochondrial membrane potential (MMP). Moreover, ATP levels were measured following lonidamine and etomoxir exposure. In addition, to define the impact of exogenous fatty acid on the cell growth and proliferation, CPT-1 activity was evaluated in the presence of palmitate (50 μM). Hexokinase and CPT-1 activities were significantly inhibited by lonidamine [600 μM] and etomoxir [100 μM] in both cell lines. Treatment of the cells with lonidamine [600 μM] resulted in a significant ATP reduction, cell viability and apoptosis, caspase-3 activity elevation, MMP reduction, and appearance of apoptosis-related morphological changes in the cells. In contrast, etomoxir [100 μM] just decreased ATP levels in both cell lines without significant cell death and apoptosis. Compared with glucose (2 g/L), palmitate intensified CPT-1 activity in both cell lines, especially in LNCaP cells. In addition, activity of CPT-1 was higher in LNCaP than PC3 cells. Our results suggest that prostate cancer cells may metabolize glucose as a source of bioenergetic pathways. ATP could also be produced by long-chain fatty acid oxidation. In addition, these data might suggest that LNCaP is more compatible with palmitate. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 56 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 2% |
| Unknown | 55 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 18% |
| Student > Master | 7 | 13% |
| Researcher | 6 | 11% |
| Professor > Associate Professor | 6 | 11% |
| Student > Bachelor | 3 | 5% |
| Other | 9 | 16% |
| Unknown | 15 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 18 | 32% |
| Medicine and Dentistry | 8 | 14% |
| Agricultural and Biological Sciences | 7 | 13% |
| Social Sciences | 2 | 4% |
| Veterinary Science and Veterinary Medicine | 1 | 2% |
| Other | 3 | 5% |
| Unknown | 17 | 30% |
Attention Score in Context
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#18,388,295
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Outputs from Tumor Biology
#1,370
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#258,279
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Outputs of similar age from Tumor Biology
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