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Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells

Overview of attention for article published in BMC Cancer, May 2015
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Title
Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells
Published in
BMC Cancer, May 2015
DOI 10.1186/s12885-015-1368-9
Pubmed ID
Authors

Anant Narayan Bhatt, Ankit Chauhan, Suchit Khanna, Yogesh Rai, Saurabh Singh, Ravi Soni, Namita Kalra, Bilikere S Dwarakanath

Abstract

Cancer cells exhibit increased glycolysis for ATP production (the Warburg effect) and macromolecular biosynthesis; it is also linked with therapeutic resistance that is generally associated with compromised respiratory metabolism. Molecular mechanisms underlying radio-resistance linked to elevated glycolysis remain incompletely understood. We stimulated glycolysis using mitochondrial respiratory modifiers (MRMs viz. di-nitro phenol, DNP; Photosan-3, PS3; Methylene blue, MB) in established human cell lines (HEK293, BMG-1 and OCT-1). Glucose utilization and lactate production, levels of glucose transporters and glycolytic enzymes were investigated as indices of glycolysis. Clonogenic survival, DNA repair and cytogenetic damage were studied as parameters of radiation response. MRMs induced the glycolysis by enhancing the levels of two important regulators of glucose metabolism GLUT-1 and HK-II and resulted in 2 fold increase in glucose consumption and lactate production. This increase in glycolysis resulted in resistance against radiation-induced cell death (clonogenic survival) in different cell lines at an absorbed dose of 5 Gy. Inhibition of glucose uptake and glycolysis (using fasentin, 2-deoxy-D-glucose and 3-bromopyruvate) in DNP treated cells failed to increase the clonogenic survival of irradiated cells, suggesting that radio-resistance linked to inhibition of mitochondrial respiration is glycolysis dependent. Elevated glycolysis also facilitated rejoining of radiation-induced DNA strand breaks by activating both non-homologous end joining (NHEJ) and homologous recombination (HR) pathways of DNA double strand break repair leading to a reduction in radiation-induced cytogenetic damage (micronuclei formation) in these cells. These findings suggest that enhanced glycolysis generally observed in cancer cells may be responsible for the radio-resistance, partly by enhancing the repair of DNA damage.

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X Demographics

The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 76 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 1%
India 1 1%
Unknown 74 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 21 28%
Student > Doctoral Student 10 13%
Researcher 9 12%
Student > Bachelor 9 12%
Student > Master 7 9%
Other 11 14%
Unknown 9 12%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 24 32%
Medicine and Dentistry 19 25%
Agricultural and Biological Sciences 7 9%
Chemistry 3 4%
Immunology and Microbiology 3 4%
Other 7 9%
Unknown 13 17%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 03 December 2015.
All research outputs
#13,433,099
of 22,800,560 outputs
Outputs from BMC Cancer
#2,973
of 8,297 outputs
Outputs of similar age
#127,359
of 264,364 outputs
Outputs of similar age from BMC Cancer
#87
of 251 outputs
Altmetric has tracked 22,800,560 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,297 research outputs from this source. They receive a mean Attention Score of 4.3. This one has gotten more attention than average, scoring higher than 62% 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 264,364 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 50% of its contemporaries.
We're also able to compare this research output to 251 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 62% of its contemporaries.