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Cell death induction by the BH3 mimetic GX15-070 in thyroid carcinoma cells

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, July 2015
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  • Good Attention Score compared to outputs of the same age (66th percentile)
  • Good Attention Score compared to outputs of the same age and source (72nd percentile)

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Title
Cell death induction by the BH3 mimetic GX15-070 in thyroid carcinoma cells
Published in
Journal of Experimental & Clinical Cancer Research, July 2015
DOI 10.1186/s13046-015-0186-x
Pubmed ID
Authors

Martina Broecker-Preuss, Jan Viehof, Holger Jastrow, Nina Becher-Boveleth, Dagmar Fuhrer, Klaus Mann

Abstract

The evasion of cell death is one of the hallmarks of cancer, contributing to both tumor progression and resistance to therapy. Dedifferentiated and anaplastic thyroid carcinomas that do not take up radioiodine are resistant to conventional anticancer treatments and patients with these tumors are difficult to treat. BH3 mimetics are a new class of drugs that target anti-apoptotic proteins of the BCL-2 family and promote cell death. The purpose of this study was to analyze the molecular effects of the BH3 mimetic GX15-070 on thyroid carcinoma cell lines and to characterize cell death induced by GX15-070. A total of 17 cell lines derived from follicular, papillary, and anaplastic thyroid carcinomas were treated with GX15-070. Cell viability was measured with MTT assay while cell cycle phase distribution and subG1 peaks were determined after propidium iodide staining. We assessed cell death via the caspase 3/7 activity, caspase cleavage products, lactate dehydrogenase (LDH) liberation assays, and a LC3 analysis by western blot. Ultrastructural changes were analysed by electron microscopy of GX15-070-treated cells. After GX15-070 treatment, the number of viable cells was decreased in all cell lines examined, with IC50 values ranging from 48nM to 3.25 μM. We observed biochemical markers of autophagic cell death and necrosis like LC3 conversion and LDH release after the GX15-070 treatment. Electron microscopy revealed several common characteristic ultrastructural changes like swelling of mitochondria, dilatation of rough endoplasmic reticulum, membrane blebbing and formation of vacuoles. GX15-070 treatment induced DNA fragmentation detected by subG1-peak induction and an arrest in G1 phase of the cell cycle. Caspase activation after GX15-070 incubation was detected but had no effect on viability of cells. With these experiments we demonstrated the efficacy of the BH3 mimetic drug GX15-070 acting against dedifferentiated thyroid carcinoma cells of various histological origins by the induction of cell death. GX15-070-treated cells underwent non-classical cell death with signs of apoptosis, autophagy and necrosis in parallel. GX15-07 and related compounds thus may be a new therapeutic option for dedifferentiated thyroid carcinoma of various histological subtypes.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Canada 1 5%
Unknown 20 95%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 4 19%
Student > Doctoral Student 2 10%
Professor 2 10%
Student > Master 2 10%
Researcher 2 10%
Other 3 14%
Unknown 6 29%
Readers by discipline Count As %
Medicine and Dentistry 5 24%
Biochemistry, Genetics and Molecular Biology 4 19%
Pharmacology, Toxicology and Pharmaceutical Science 3 14%
Immunology and Microbiology 1 5%
Chemistry 1 5%
Other 0 0%
Unknown 7 33%
Attention Score in Context

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 26 November 2020.
All research outputs
#8,261,140
of 25,371,288 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#536
of 2,378 outputs
Outputs of similar age
#90,319
of 275,271 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#5
of 25 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one has received more attention than most of these and is in the 66th percentile.
So far Altmetric has tracked 2,378 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done well, scoring higher than 76% 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 275,271 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 66% of its contemporaries.
We're also able to compare this research output to 25 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 72% of its contemporaries.