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The glutamate transport inhibitor DL-Threo-β-Benzyloxyaspartic acid (DL-TBOA) differentially affects SN38- and oxaliplatin-induced death of drug-resistant colorectal cancer cells

Overview of attention for article published in BMC Cancer, May 2015
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  • Good Attention Score compared to outputs of the same age (71st percentile)

Mentioned by

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2 tweeters
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1 patent

Citations

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11 Dimensions

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32 Mendeley
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Title
The glutamate transport inhibitor DL-Threo-β-Benzyloxyaspartic acid (DL-TBOA) differentially affects SN38- and oxaliplatin-induced death of drug-resistant colorectal cancer cells
Published in
BMC Cancer, May 2015
DOI 10.1186/s12885-015-1405-8
Pubmed ID
Authors

Elena Pedraz-Cuesta, Sandra Christensen, Anders A. Jensen, Niels Frank Jensen, Lennart Bunch, Maria Unni Romer, Nils Brünner, Jan Stenvang, Stine Falsig Pedersen

Abstract

Colorectal cancer (CRC) is a leading cause of cancer death globally and new biomarkers and treatments are severely needed. Here, we employed HCT116 and LoVo human CRC cells made resistant to either SN38 or oxaliplatin, to investigate whether altered expression of the high affinity glutamate transporters Solute Carrier (SLC)-1A1 and -1A3 (EAAT3, EAAT1) is associated with the resistant phenotypes. Analyses included real-time quantitative PCR, immunoblotting and immunofluorescence analyses, radioactive tracer flux measurements, and biochemical analyses of cell viability and glutathione content. Results were evaluated using one- and two-way ANOVA and Students two-tailed t-test, as relevant. In SN38-resistant HCT116 and LoVo cells, SLC1A1 expression was down-regulated ~60 % and up-regulated ~4-fold, respectively, at both mRNA and protein level, whereas SLC1A3 protein was undetectable. The changes in SLC1A1 expression were accompanied by parallel changes in DL-Threo-β-Benzyloxyaspartic acid (TBOA)-sensitive, UCPH101-insensitive [(3)H]-D-Aspartate uptake, consistent with increased activity of SLC1A1 (or other family members), yet not of SLC1A3. DL-TBOA co-treatment concentration-dependently augmented loss of cell viability induced by SN38, while strongly counteracting that induced by oxaliplatin, in both HCT116 and LoVo cells. This reflected neither altered expression of the oxaliplatin transporter Cu(2+)-transporter-1 (CTR1), nor changes in cellular reduced glutathione (GSH), although HCT116 cell resistance per se correlated with increased cellular GSH. DL-TBOA did not significantly alter cellular levels of p21, cleaved PARP-1, or phospho-Retinoblastoma protein, yet altered SLC1A1 subcellular localization, and reduced chemotherapy-induced p53 induction. SLC1A1 expression and glutamate transporter activity are altered in SN38-resistant CRC cells. Importantly, the non-selective glutamate transporter inhibitor DL-TBOA reduces chemotherapy-induced p53 induction and augments CRC cell death induced by SN38, while attenuating that induced by oxaliplatin. These findings may point to novel treatment options in treatment-resistant CRC.

Twitter Demographics

The data shown below were collected from the profiles of 2 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 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Denmark 1 3%
Unknown 31 97%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 7 22%
Student > Master 6 19%
Researcher 3 9%
Other 3 9%
Professor 2 6%
Other 4 13%
Unknown 7 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 22%
Agricultural and Biological Sciences 6 19%
Medicine and Dentistry 4 13%
Pharmacology, Toxicology and Pharmaceutical Science 2 6%
Nursing and Health Professions 2 6%
Other 3 9%
Unknown 8 25%

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 24 January 2019.
All research outputs
#4,864,452
of 17,356,510 outputs
Outputs from BMC Cancer
#1,191
of 6,308 outputs
Outputs of similar age
#65,864
of 237,774 outputs
Outputs of similar age from BMC Cancer
#1
of 1 outputs
Altmetric has tracked 17,356,510 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 6,308 research outputs from this source. They receive a mean Attention Score of 4.1. This one has done well, scoring higher than 80% 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 237,774 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 71% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them