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Thioridazine enhances sensitivity to carboplatin in human head and neck cancer cells through downregulation of c-FLIP and Mcl-1 expression

Overview of attention for article published in Cell Death & Disease, February 2017
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (77th percentile)
  • Good Attention Score compared to outputs of the same age and source (71st percentile)

Mentioned by

news
1 news outlet

Citations

dimensions_citation
19 Dimensions

Readers on

mendeley
25 Mendeley
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Title
Thioridazine enhances sensitivity to carboplatin in human head and neck cancer cells through downregulation of c-FLIP and Mcl-1 expression
Published in
Cell Death & Disease, February 2017
DOI 10.1038/cddis.2017.8
Pubmed ID
Authors

Seung Un Seo, Hyuk Ki Cho, Kyoung-jin Min, Seon Min Woo, Shin Kim, Jong-Wook Park, Sang Hyun Kim, Yung Hyun Choi, Young Sam Keum, Jin Won Hyun, Hyun Ho Park, Sang-Han Lee, Dong Eun Kim, Taeg Kyu Kwon

Abstract

Carboplatin is a less toxic analog of cisplatin, but carboplatin also has side effects, including bone marrow suppression. Therefore, to improve the capacity of the anticancer activity of carboplatin, we investigated whether combined treatment with carboplatin and thioridazine, which has antipsychotic and anticancer activities, has a synergistic effect on apoptosis. Combined treatment with carboplatin and thioridazine markedly induced caspase-mediated apoptosis in head and neck squamous cell carcinoma (AMC-HN4) cells. Combined treatment with carboplatin and thioridazine induced downregulation of Mcl-1 and c-FLIP expression. Ectopic expression of Mcl-1 and c-FLIP inhibited carboplatin plus thioridazine-induced apoptosis. We found that augmentation of proteasome activity had a critical role in downregulation of Mcl-1 and c-FLIP expression at the post-translational level in carboplatin plus thioridazine-treated cells. Furthermore, carboplatin plus thioridazine induced upregulation of the expression of proteasome subunit alpha 5 (PSMA5) through mitochondrial reactive oxygen species (ROS)-dependent nuclear factor E2-related factor 2 (Nrf2) activation. In addition, combined treatment with carboplatin and thioridazine markedly induced apoptosis in human breast carcinoma (MDA-MB231) and glioma (U87MG) cells, but not in human normal mesangial cells and normal human umbilical vein cells (EA.hy926). Collectively, our study demonstrates that combined treatment with carboplatin and thioridazine induces apoptosis through proteasomal degradation of Mcl-1 and c-FLIP by upregulation of Nrf2-dependent PSMA5 expression.

Mendeley readers

The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 25 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 16%
Student > Doctoral Student 4 16%
Student > Ph. D. Student 3 12%
Student > Bachelor 3 12%
Other 2 8%
Other 4 16%
Unknown 5 20%
Readers by discipline Count As %
Medicine and Dentistry 5 20%
Biochemistry, Genetics and Molecular Biology 4 16%
Agricultural and Biological Sciences 4 16%
Pharmacology, Toxicology and Pharmaceutical Science 2 8%
Psychology 1 4%
Other 3 12%
Unknown 6 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 10 February 2017.
All research outputs
#2,032,552
of 12,861,156 outputs
Outputs from Cell Death & Disease
#782
of 2,962 outputs
Outputs of similar age
#71,778
of 342,820 outputs
Outputs of similar age from Cell Death & Disease
#21
of 110 outputs
Altmetric has tracked 12,861,156 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,962 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has gotten more attention than average, scoring higher than 64% 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 342,820 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 77% of its contemporaries.
We're also able to compare this research output to 110 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 71% of its contemporaries.