| Title |
A heterometallic ruthenium–gold complex displays antiproliferative, antimigratory, and antiangiogenic properties and inhibits metastasis and angiogenesis-associated proteases in renal cancer
|
|---|---|
| Published in |
JBIC Journal of Biological Inorganic Chemistry, March 2018
|
| DOI | 10.1007/s00775-018-1546-8 |
| Pubmed ID | |
| Authors |
Benelita T. Elie, Yuriy Pechenyy, Fathema Uddin, María Contel |
| Abstract |
Heterobimetallic compounds are designed to harness chemotherapeutic traits of distinct metal species into a single molecule. The ruthenium-gold (Ru-Au) family of compounds based on Au-N-heterocyclic carbene (NHC) fragments [Cl2(p-cymene)Ru(μ-dppm)Au(NHC)]ClO4 was conceived to combine the known antiproliferative and cytotoxic properties of Au-NHC-based compounds and the antimigratory, antimetastatic, and antiangiogenic characteristic of specific Ru-based compounds. Following recent studies of the anticancer efficacies of these Ru-Au-NHC complexes with promising potential as chemotherapeutics against colorectal, and renal cancers in vitro, we report here on the mechanism of a selected compound, [Cl2(p-cymene)Ru(μ-dppm)Au(IMes)]ClO4 (RANCE-1, 1). The studies were carried out in vitro using a human clear cell renal carcinoma cell line (Caki-1). These studies indicate that bimetallic compound RANCE-1 (1) is significantly more cytotoxic than the Ru (2) or Au (3) monometallic derivatives. RANCE-1 significantly inhibits migration, invasion, and angiogenesis, which are essential for metastasis. RANCE-1 was found to disturb pericellular proteolysis by inhibiting cathepsins, and the metalloproteases MMP and ADAM which play key roles in the etiopathogenesis of cancer. RANCE-1 also inhibits the mitochondrial protein TrxR that is often overexpressed in cancer cells and facilitates apoptosis evasion. We found that while auranofin perturbed migration and invasion to similar degrees as RANCE-1 (1) in Caki-1 renal cancer cells, RANCE-1 (1) inhibited antiangiogenic formation and VEGF expression. We found that auranofin and RANCE-1 (1) have distinct proteolytic profiles. In summary, RANCE-1 constitutes a very promising candidate for further preclinical evaluations in renal cancer. |
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 % |
|---|---|---|
| United States | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Scientists | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 42 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 17% |
| Student > Bachelor | 4 | 10% |
| Student > Master | 4 | 10% |
| Professor > Associate Professor | 4 | 10% |
| Student > Doctoral Student | 3 | 7% |
| Other | 7 | 17% |
| Unknown | 13 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 18 | 43% |
| Biochemistry, Genetics and Molecular Biology | 4 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
| Unspecified | 1 | 2% |
| Physics and Astronomy | 1 | 2% |
| Other | 3 | 7% |
| Unknown | 14 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 28 September 2018.
All research outputs
#14,001,230
of 23,842,189 outputs
Outputs from JBIC Journal of Biological Inorganic Chemistry
#418
of 664 outputs
Outputs of similar age
#173,555
of 333,803 outputs
Outputs of similar age from JBIC Journal of Biological Inorganic Chemistry
#5
of 14 outputs
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So far Altmetric has tracked 664 research outputs from this source. They receive a mean Attention Score of 3.5. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
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We're also able to compare this research output to 14 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.