| Title |
DNA-PK inhibition by NU7441 sensitizes breast cancer cells to ionizing radiation and doxorubicin
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, November 2013
|
| DOI | 10.1007/s10549-013-2785-6 |
| Pubmed ID | |
| Authors |
Wojciech M. Ciszewski, Michele Tavecchio, Jarosław Dastych, Nicola J. Curtin |
| Abstract |
DNA-dependent protein kinase (DNA-PK) plays a key role in the repair of DNA double-strand breaks (DSBs) that are probably the most deleterious form of DNA damage. Inhibition of DNA-PK has been considered as an attractive approach to decrease resistance to therapeutically induced DNA DSBs. Ionizing radiation (IR) and doxorubicin, which induce DSBs, are used in the treatment of breast cancer. We determined the cellular concentration of DNA-PK and other DSB-activated kinases: ATM and ATR and the effect of DNA-PK inhibition by NU7441 on DNA repair, cell cycle, and survival after IR or doxorubicin treatment in three human breast cancer cell lines (MCF-7, MDA-MB-231, and T47D) representing different breast cancer subtypes. T47D cells had the highest expression of DNA-PKcs, ATM, and ATR and the most rapid rate of DNA DSB repair. IR caused a 10- to 16-fold increase in DNA-PK activity and two to threefold induction of ATM in all 3 cell lines. NU7441 inhibited IR-induced DNA-PK activity in all cell lines with IC50s in the range 0.17-0.25 μM. NU7441 retarded the repair of DSB and significantly increased the sensitivity of all cell lines to IR (4- to 12-fold) and doxorubicin (3- to 13-fold). The greatest sensitization by NU7441 was observed in MDA-MB-231 cells. NU7441 affected the cell cycle distribution in all studied cell lines; increasing accumulation of cells in G2/M phase after DNA damage. Our data indicate that DNA-PK might be an effective target for chemo- and radio-potentiation in breast cancer and suggest that further development of DNA-PK inhibitors for clinical use is warranted. |
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 % |
|---|---|---|
| Spain | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 90 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 90 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 20 | 22% |
| Student > Master | 14 | 16% |
| Student > Bachelor | 13 | 14% |
| Researcher | 7 | 8% |
| Professor > Associate Professor | 6 | 7% |
| Other | 15 | 17% |
| Unknown | 15 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 21 | 23% |
| Biochemistry, Genetics and Molecular Biology | 21 | 23% |
| Medicine and Dentistry | 18 | 20% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 3% |
| Chemistry | 2 | 2% |
| Other | 4 | 4% |
| Unknown | 21 | 23% |
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 19 December 2019.
All research outputs
#6,941,350
of 22,760,687 outputs
Outputs from Breast Cancer Research and Treatment
#1,513
of 4,652 outputs
Outputs of similar age
#83,504
of 307,105 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#31
of 71 outputs
Altmetric has tracked 22,760,687 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 4,652 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one has gotten more attention than average, scoring higher than 66% 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 307,105 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 71% of its contemporaries.
We're also able to compare this research output to 71 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 54% of its contemporaries.