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Dichloroacetate restores drug sensitivity in paclitaxel-resistant cells by inducing citric acid accumulation

Overview of attention for article published in Molecular Cancer, March 2015
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Title
Dichloroacetate restores drug sensitivity in paclitaxel-resistant cells by inducing citric acid accumulation
Published in
Molecular Cancer, March 2015
DOI 10.1186/s12943-015-0331-3
Pubmed ID
Authors

Xiang Zhou, Ruohua Chen, Zhenhai Yu, Rui Li, Jiajin Li, Xiaoping Zhao, Shaoli Song, Jianjun Liu, Gang Huang

Abstract

The Warburg effect describes the increased reliance of tumor cells on glycolysis for ATP generation. Mitochondrial respiratory defect is thought to be an important factor leading to the Warburg effect in some types of tumor cells. Consequently, there is growing interest in developing anti-cancer drugs that target mitochondria. One example is dichloroacetate (DCA) that stimulates mitochondria through inhibition of pyruvate dehydrogenase kinase. We investigated the anti-cancer activity of DCA using biochemical and isotopic tracing methods. We observed that paclitaxel-resistant cells contained decreased levels of citric acid and sustained mitochondrial respiratory defect. DCA specifically acted on cells with mitochondrial respiratory defect to reverse paclitaxel resistance. DCA could not effectively activate oxidative respiration in drug-resistant cells, but induced higher levels of citrate accumulation, which led to inhibition of glycolysis and inactivation of P-glycoprotein. The abilityof DCA to target cells with mitochondrial respiratory defect and restore paclitaxel sensitivity by inducing citrate accumulation supports further preclinical development.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 19%
Student > Bachelor 5 16%
Researcher 3 10%
Student > Doctoral Student 2 6%
Student > Master 2 6%
Other 6 19%
Unknown 7 23%
Readers by discipline Count As %
Medicine and Dentistry 7 23%
Biochemistry, Genetics and Molecular Biology 6 19%
Agricultural and Biological Sciences 6 19%
Computer Science 1 3%
Immunology and Microbiology 1 3%
Other 3 10%
Unknown 7 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 23 May 2015.
All research outputs
#4,268,962
of 5,133,091 outputs
Outputs from Molecular Cancer
#526
of 616 outputs
Outputs of similar age
#142,268
of 172,636 outputs
Outputs of similar age from Molecular Cancer
#41
of 43 outputs
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So far Altmetric has tracked 616 research outputs from this source. They receive a mean Attention Score of 3.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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