| Title |
Carmustine enhances the anticancer activity of selenite in androgen-independent prostate cancer cells
|
|---|---|
| Published in |
Cancer Management and Research, November 2012
|
| DOI | 10.2147/cmar.s38022 |
| Pubmed ID | |
| Authors |
Vijayalakshmi Thamilselvan, Mani Menon, Sivagnanam Thamilselvan |
| Abstract |
Apoptosis is one of the major mechanisms targeted in the development of therapies against various cancers, including prostate cancer. Resistance to chemotherapy poses a significant problem for the effective treatment of androgen-independent (hormone-refractory) prostate cancer. Although high concentrations of sodium selenite exert strong anticarcinogenic effects in several cell culture systems and animal models, the therapeutic potential of selenite in patients with advanced or metastatic prostate cancer is extremely limited by the genotoxicity of high-dose selenite. We examined the ability of nontoxic concentrations of selenite to promote apoptosis and inhibit proliferation in carmustine-sensitized androgen-independent human prostate cancer cells. Androgen-dependent LNCaP cells exhibited a significant decrease in cell viability when exposed to nontoxic concentrations of selenite, whereas androgen-independent PC-3 and DU145 cells showed a significant decrease in cell viability only at higher concentrations. Treatment of PC-3 cells with a combination of nontoxic selenite and carmustine resulted in greater increases in cytotoxicity, reactive oxygen species generation, growth inhibition, apoptosis, and DNA double-strand breaks, with concomitant decreases in DNA synthesis, glutathione, glutathione reductase, and antiapoptotic proteins. Combination treatment with carmustine and selenite triggered caspase-dependent apoptosis in PC-3 cells, which was not apparent when these cells were treated with selenite or carmustine alone. Genotoxicity in normal prostate epithelial cells was completely absent in the combination treatment of carmustine and selenite. In addition, carmustine decreased the induction of DNA double strand breaks by high-dose selenite in normal prostate epithelial cells. This is the first study to demonstrate that a nontoxic dose of selenite, in combination with carmustine, significantly induces apoptosis and growth inhibition in androgen-independent prostate cancer cells without causing undesirable genotoxicity in normal prostate epithelial cells, suggesting that this combination therapy may be a promising therapeutic approach in the treatment of patients with metastatic hormone-refractory prostate cancer. |
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 % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 9 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 9 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 3 | 33% |
| Student > Doctoral Student | 2 | 22% |
| Student > Bachelor | 1 | 11% |
| Researcher | 1 | 11% |
| Unknown | 2 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 4 | 44% |
| Chemistry | 2 | 22% |
| Agricultural and Biological Sciences | 1 | 11% |
| Unknown | 2 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 November 2012.
All research outputs
#20,823,121
of 25,584,565 outputs
Outputs from Cancer Management and Research
#1,116
of 2,067 outputs
Outputs of similar age
#158,651
of 202,619 outputs
Outputs of similar age from Cancer Management and Research
#3
of 6 outputs
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