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The SMAC mimetic BV6 sensitizes colorectal cancer cells to ionizing radiation by interfering with DNA repair processes and enhancing apoptosis

Overview of attention for article published in Radiation Oncology, September 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

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1 news outlet
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3 X users

Citations

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30 Dimensions

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36 Mendeley
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Title
The SMAC mimetic BV6 sensitizes colorectal cancer cells to ionizing radiation by interfering with DNA repair processes and enhancing apoptosis
Published in
Radiation Oncology, September 2015
DOI 10.1186/s13014-015-0507-4
Pubmed ID
Authors

Stephanie Hehlgans, Julius Oppermann, Sebastian Reichert, Simone Fulda, Claus Rödel, Franz Rödel

Abstract

In the present study, we aimed to investigate the effect of counteracting inhibitor of apoptosis (IAP) proteins using the small molecule Second Mitochondria-derived Activator of Caspase (SMAC) mimetic BV6 in combination with ionizing radiation on apoptosis, cell cycle regulation, DNA double-strand break (DSB) repair, three-dimensional (3D) clonogenic survival and expression of IAPs in colorectal carcinoma cells. Colorectal cancer cell lines (HCT-15, HT-29, SW480) were subjected to BV6 treatment (0-4 μM) with or without irradiation (2-8 Gy, single dose) followed by MTT, Caspase 3/7 activity, γH2AX/53BP1 foci assays, AnnexinV staining, cell cycle analysis, 3D colony forming assays and Western blotting (cellular IAP1 (cIAP1) and cIAP2, Survivin, X-linked IAP (XIAP)). BV6 treatment decreased cell viability and significantly increased irradiation-induced apoptosis as analyzed by Caspase 3/7 activity, AnnexinV-positive and subG1 phase cells. While basal 3D clonogenic survival was decreased in a cell line-dependent manner, BV6 significantly enhanced cellular radiosensitivity of all cell lines in a concentration-dependent manner and increased the number of radiation-induced γH2AX/53BP1-positive foci. Western blot analysis revealed a markedly reduced cIAP1 expression at 4 h after BV6 treatment in all cell lines, a substantial reduction of XIAP expression in SW480 and HT-29 cells at 24 h and a slightly decreased cIAP2 expression in HCT-15 cells at 48 h after treatment. Moreover, single or double knockdown of cIAP1 and XIAP resulted in significantly increased residual γH2AX/53BP1-positive foci 24 h after 2 Gy and radiosensitization relative to control small interfering RNA (siRNA)-treated cells. The SMAC mimetic BV6 induced apoptosis and hampered DNA damage repair to radiosensitize 3D grown colorectal cancer cells. Our results demonstrate IAP targeting as a promising strategy to counteract radiation resistance of colorectal cancer cells.

X Demographics

X Demographics

The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 6%
Unknown 34 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 22%
Other 5 14%
Student > Doctoral Student 4 11%
Student > Master 4 11%
Researcher 3 8%
Other 3 8%
Unknown 9 25%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 22%
Medicine and Dentistry 7 19%
Biochemistry, Genetics and Molecular Biology 6 17%
Chemical Engineering 1 3%
Unspecified 1 3%
Other 3 8%
Unknown 10 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 August 2018.
All research outputs
#2,683,883
of 22,828,180 outputs
Outputs from Radiation Oncology
#64
of 2,057 outputs
Outputs of similar age
#38,055
of 272,396 outputs
Outputs of similar age from Radiation Oncology
#1
of 62 outputs
Altmetric has tracked 22,828,180 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,057 research outputs from this source. They receive a mean Attention Score of 2.7. This one has done particularly well, scoring higher than 96% 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 272,396 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 85% of its contemporaries.
We're also able to compare this research output to 62 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 98% of its contemporaries.