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Oncotarget

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ONC201 kills breast cancer cells in vitro by targeting mitochondria

Overview of attention for article published in Oncotarget, April 2018
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (95th percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

Mentioned by

news
6 news outlets
blogs
1 blog
twitter
9 tweeters
patent
4 patents

Citations

dimensions_citation
43 Dimensions

Readers on

mendeley
47 Mendeley
Title
ONC201 kills breast cancer cells in vitro by targeting mitochondria
Published in
Oncotarget, April 2018
DOI 10.18632/oncotarget.24862
Pubmed ID
Authors

Yoshimi Endo Greer, Natalie Porat-Shliom, Kunio Nagashima, Christina Stuelten, Dan Crooks, Vishal N. Koparde, Samuel F. Gilbert, Celia Islam, Ashley Ubaldini, Yun Ji, Luca Gattinoni, Ferri Soheilian, Xiantao Wang, Markus Hafner, Jyoti Shetty, Bao Tran, Parthav Jailwala, Maggie Cam, Martin Lang, Donna Voeller, William C. Reinhold, Vinodh Rajapakse, Yves Pommier, Roberto Weigert, W. Marston Linehan, Stanley Lipkowitz

Abstract

We report a novel mechanism of action of ONC201 as a mitochondria-targeting drug in cancer cells. ONC201 was originally identified as a small molecule that induces transcription of TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cancer cells by activating TRAIL death receptors. In this study, we examined ONC201 toxicity on multiple human breast and endometrial cancer cell lines. ONC201 attenuated cell viability in all cancer cell lines tested. Unexpectedly, ONC201 toxicity was not dependent on either TRAIL receptors nor caspases. Time-lapse live cell imaging revealed that ONC201 induces cell membrane ballooning followed by rupture, distinct from the morphology of cells undergoing apoptosis. Further investigation found that ONC201 induces phosphorylation of AMP-dependent kinase and ATP loss. Cytotoxicity and ATP depletion were significantly enhanced in the absence of glucose, suggesting that ONC201 targets mitochondrial respiration. Further analysis indicated that ONC201 indirectly inhibits mitochondrial respiration. Confocal and electron microscopic analysis demonstrated that ONC201 triggers mitochondrial structural damage and functional impairment. Moreover, ONC201 decreased mitochondrial DNA (mtDNA). RNAseq analysis revealed that ONC201 suppresses expression of multiple mtDNA-encoded genes and nuclear-encoded mitochondrial genes involved in oxidative phosphorylation and other mitochondrial functions. Importantly, fumarate hydratase deficient cancer cells and multiple cancer cell lines with reduced amounts of mtDNA were resistant to ONC201. These results indicate that cells not dependent on mitochondrial respiration are ONC201-resistant. Our data demonstrate that ONC201 kills cancer cells by disrupting mitochondrial function and further suggests that cancer cells that are dependent on glycolysis will be resistant to ONC201.

Twitter Demographics

The data shown below were collected from the profiles of 9 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 47 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 23%
Researcher 11 23%
Student > Master 4 9%
Student > Bachelor 4 9%
Student > Postgraduate 3 6%
Other 5 11%
Unknown 9 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 21%
Medicine and Dentistry 6 13%
Pharmacology, Toxicology and Pharmaceutical Science 5 11%
Agricultural and Biological Sciences 5 11%
Business, Management and Accounting 2 4%
Other 7 15%
Unknown 12 26%

Attention Score in Context

This research output has an Altmetric Attention Score of 61. 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 14 September 2021.
All research outputs
#485,584
of 19,722,829 outputs
Outputs from Oncotarget
#160
of 13,855 outputs
Outputs of similar age
#13,654
of 294,183 outputs
Outputs of similar age from Oncotarget
#9
of 499 outputs
Altmetric has tracked 19,722,829 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 13,855 research outputs from this source. They receive a mean Attention Score of 4.9. This one has done particularly well, scoring higher than 98% 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 294,183 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 499 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.