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A Novel Anticancer Gold(III) Dithiocarbamate Compound Inhibits the Activity of a Purified 20S Proteasome and 26S Proteasome in Human Breast Cancer Cell Cultures and Xenografts

Overview of attention for article published in Cancer Research, November 2006
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (83rd percentile)
  • High Attention Score compared to outputs of the same age and source (87th percentile)

Mentioned by

patent
3 patents
facebook
1 Facebook page

Citations

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227 Dimensions

Readers on

mendeley
93 Mendeley
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Title
A Novel Anticancer Gold(III) Dithiocarbamate Compound Inhibits the Activity of a Purified 20S Proteasome and 26S Proteasome in Human Breast Cancer Cell Cultures and Xenografts
Published in
Cancer Research, November 2006
DOI 10.1158/0008-5472.can-06-3017
Pubmed ID
Authors

Vesna Milacic, Di Chen, Luca Ronconi, Kristin R. Landis-Piwowar, Dolores Fregona, Q. Ping Dou

Abstract

Although cisplatin has been used for decades to treat human cancer, some toxic side effects and resistance are observed. It has been suggested that gold(III) complexes, containing metal centers isoelectronic and isostructural to cisplatin, are promising anticancer drugs. Gold(III) dithiocarbamate complexes were shown to exhibit in vitro cytotoxicity, comparable with and even greater than cisplatin; however, the involved mechanism of action remained unknown. Because we previously reported that copper(II) dithiocarbamates are potent proteasome inhibitors, we hypothesized that gold(III) dithiocarbamate complexes could suppress tumor growth via direct inhibition of the proteasome activity. Here, for the first time, we report that a synthetic gold(III) dithiocarbamate (compound 2) potently inhibits the activity of a purified rabbit 20S proteasome and 26S proteasome in intact highly metastatic MDA-MB-231 breast cancer cells, resulting in the accumulation of ubiquitinated proteins and the proteasome target protein p27 and induction of apoptosis. The compound 2-mediated proteasome inhibition and apoptosis induction were completely blocked by addition of a reducing agent DTT or N-acetyl-L-cysteine, showing that process of oxidation is required for proteasome inhibition by compound 2. Treatment of MDA-MB-231 breast tumor-bearing nude mice with compound 2 resulted in significant inhibition of tumor growth, associated with proteasome inhibition and massive apoptosis induction in vivo. Our findings reveal the proteasome as a primary target for gold(III) dithiocarbamates and support the idea for their potential use as anticancer therapeutics.

Mendeley readers

The data shown below were compiled from readership statistics for 93 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Malaysia 1 1%
Netherlands 1 1%
France 1 1%
Italy 1 1%
Austria 1 1%
Czechia 1 1%
United Kingdom 1 1%
Saudi Arabia 1 1%
Unknown 85 91%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 27 29%
Student > Master 17 18%
Student > Bachelor 16 17%
Student > Doctoral Student 6 6%
Student > Postgraduate 6 6%
Other 14 15%
Unknown 7 8%
Readers by discipline Count As %
Chemistry 44 47%
Agricultural and Biological Sciences 14 15%
Biochemistry, Genetics and Molecular Biology 12 13%
Medicine and Dentistry 7 8%
Pharmacology, Toxicology and Pharmaceutical Science 3 3%
Other 5 5%
Unknown 8 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 26 September 2012.
All research outputs
#1,704,157
of 10,623,464 outputs
Outputs from Cancer Research
#1,644
of 9,919 outputs
Outputs of similar age
#17,749
of 111,708 outputs
Outputs of similar age from Cancer Research
#5
of 41 outputs
Altmetric has tracked 10,623,464 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 9,919 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one has done well, scoring higher than 83% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 111,708 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 83% of its contemporaries.
We're also able to compare this research output to 41 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 87% of its contemporaries.