| Title |
Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status
|
|---|---|
| Published in |
Investigational New Drugs, July 2017
|
| DOI | 10.1007/s10637-017-0488-2 |
| Pubmed ID | |
| Authors |
Mohamed Wehbe, Cody Lo, Ada W. Y. Leung, Wieslawa H. Dragowska, Gemma M. Ryan, Marcel B. Bally |
| Abstract |
Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC50 ~ 1 μM platinum) and insensitive (IC50 > 5 μM platinum) cell lines. Furthermore, copper complexes of DDC, Pyr and 8-HQ had greater therapeutic activity compared to the copper-free ligands in all cell lines; whereas the copper-dependent activities of Plum and CQ were cell-line specific. Four of the copper complexes (Cu(DDC)2, Cu(Pyr)2, Cu(Plum)2 and Cu(8-HQ)2) showed IC50 values less than that of cisplatin in all tested cell lines. The complex copper DDC (Cu(DDC)2) was selected for in vivo evaluation due to its low nano-molar range activity in vitro and the availability of an injectable liposomal formulation. Liposomal (Cu(DDC)2) was tested in a fast-growing platinum-resistant A2780-CP ovarian xenograft model and was found to achieve a statistically significant reduction (50%; p < 0.05) in tumour size. This work supports the potential use of copper-based therapeutics to treat cancers that are insensitive to platinum drugs. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 2 | 50% |
| United States | 1 | 25% |
| Unknown | 1 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 50% |
| Practitioners (doctors, other healthcare professionals) | 1 | 25% |
| Scientists | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 55 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 55 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 9 | 16% |
| Student > Master | 6 | 11% |
| Student > Doctoral Student | 6 | 11% |
| Researcher | 5 | 9% |
| Student > Ph. D. Student | 5 | 9% |
| Other | 8 | 15% |
| Unknown | 16 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 13 | 24% |
| Biochemistry, Genetics and Molecular Biology | 9 | 16% |
| Agricultural and Biological Sciences | 4 | 7% |
| Medicine and Dentistry | 3 | 5% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
| Other | 3 | 5% |
| Unknown | 21 | 38% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. 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 07 August 2018.
All research outputs
#7,477,538
of 22,990,068 outputs
Outputs from Investigational New Drugs
#326
of 1,173 outputs
Outputs of similar age
#118,996
of 314,579 outputs
Outputs of similar age from Investigational New Drugs
#2
of 11 outputs
Altmetric has tracked 22,990,068 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 1,173 research outputs from this source. They receive a mean Attention Score of 4.7. This one has gotten more attention than average, scoring higher than 72% 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 314,579 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 61% of its contemporaries.
We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 81% of its contemporaries.