| Title |
Identification of capsazepine as a novel inhibitor of system xc− and cancer-induced bone pain
|
|---|---|
| Published in |
Journal of Pain Research, April 2017
|
| DOI | 10.2147/jpr.s125045 |
| Pubmed ID | |
| Authors |
Jennifer Fazzari, Matthew D Balenko, Natalie Zacal, Gurmit Singh |
| Abstract |
The cystine/glutamate antiporter has been implicated in a variety of cancers as a major mediator of redox homeostasis. The excess glutamate secreted by this transporter in aggressive cancer cells has been associated with cancer-induced bone pain (CIBP) from distal breast cancer metastases. High-throughput screening of small molecule inhibitors of glutamate release from breast cancer cells identified several potential compounds. One such compound, capsazepine (CPZ), was confirmed to inhibit the functional unit of system xc(-) (xCT) through its ability to block uptake of its radiolabeled substrate, cystine. Blockade of this antiporter induced production of reactive oxygen species (ROS) within 4 hours and induced cell death within 48 hours at concentrations exceeding 25 μM. Furthermore, cell death and ROS production were significantly reduced by co-treatment with N-acetylcysteine, suggesting that CPZ toxicity is associated with ROS-induced cell death. These data suggest that CPZ can modulate system xc(-) activity in vitro and this translates into antinociception in an in vivo model of CIBP where systemic administration of CPZ successfully delayed the onset and reversed CIBP-induced nociceptive behaviors resulting from intrafemoral MDA-MB-231 tumors. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Malaysia | 1 | 5% |
| Unknown | 21 | 95% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 4 | 18% |
| Researcher | 4 | 18% |
| Student > Ph. D. Student | 3 | 14% |
| Student > Doctoral Student | 2 | 9% |
| Student > Master | 2 | 9% |
| Other | 2 | 9% |
| Unknown | 5 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 23% |
| Medicine and Dentistry | 4 | 18% |
| Chemistry | 2 | 9% |
| Agricultural and Biological Sciences | 2 | 9% |
| Unspecified | 1 | 5% |
| Other | 2 | 9% |
| Unknown | 6 | 27% |
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 02 May 2017.
All research outputs
#18,546,002
of 22,968,808 outputs
Outputs from Journal of Pain Research
#1,402
of 1,757 outputs
Outputs of similar age
#235,458
of 309,601 outputs
Outputs of similar age from Journal of Pain Research
#57
of 65 outputs
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