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Vitamin C enhances epigenetic modifications induced by 5-azacytidine and cell cycle arrest in the hepatocellular carcinoma cell lines HLE and Huh7

Overview of attention for article published in Clinical Epigenetics, April 2016
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  • Above-average Attention Score compared to outputs of the same age (64th percentile)

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Title
Vitamin C enhances epigenetic modifications induced by 5-azacytidine and cell cycle arrest in the hepatocellular carcinoma cell lines HLE and Huh7
Published in
Clinical Epigenetics, April 2016
DOI 10.1186/s13148-016-0213-6
Pubmed ID
Authors

Sahar Olsadat Sajadian, Chaturvedula Tripura, Fazel Sahraneshin Samani, Marc Ruoss, Steven Dooley, Hossein Baharvand, Andreas K. Nussler

Abstract

5-Azacytidine (5-AZA), a DNA methyl transferase inhibitor, is a clinically used epigenetic drug for cancer therapy. Recently, we have shown that 5-AZA upregulates ten-eleven translocation (TET) protein expression in hepatocellular carcinoma (HCC) cells, which induce active demethylation. Vitamin C facilitates TET activity and enhances active demethylation. The aim of this study is to investigate whether vitamin C is able to enhance the effect of 5-AZA on active demethylation and to evaluate its consequence in HCC cell lines. HCC cell lines (Huh7 and HLE) were treated with 5-AZA and vitamin C. After 48 h of treatment, viability (resazurin conversion), toxicity (lactose dehydrogenase (LDH) release), and proliferation ((proliferating cell nuclear antigen (PCNA)) of single- and combined-treated cells were assessed. The effect of the treatment on 5-hydroxymethylcytosine (5hmC) intensity (immunofluorescence (IF) staining), TET, Snail, GADD45B, and P21 mRNA (real-time PCR) and protein expression (Western blot) were investigated. Our results indicated that vitamin C enhances the anti-proliferative and apoptotic effect of 5-AZA in HCC cell lines. By further analyzing the events leading to cell cycle arrest, we have shown for the first time in HCC that the combination of 5-AZA and vitamin C leads to an enhanced downregulation of Snail expression, a key transcription factor governing epithelial-mesenchymal transition (EMT) process, and cell cycle arrest. We conclude that when combined with 5-AZA, vitamin C enhances TET activity in HCC cells, leading to induction of active demethylation. An increase in P21 expression as a consequence of downregulation of Snail accompanied by the induction of GADD45B expression is the main mechanism leading to cell cycle arrest in HCCs.

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X Demographics

The data shown below were collected from the profiles of 6 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 80 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 80 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 18 23%
Researcher 11 14%
Student > Bachelor 10 13%
Student > Ph. D. Student 9 11%
Student > Doctoral Student 5 6%
Other 13 16%
Unknown 14 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 20 25%
Agricultural and Biological Sciences 15 19%
Medicine and Dentistry 11 14%
Pharmacology, Toxicology and Pharmaceutical Science 6 8%
Nursing and Health Professions 3 4%
Other 5 6%
Unknown 20 25%
Attention Score in Context

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 27 May 2016.
All research outputs
#7,234,904
of 22,867,327 outputs
Outputs from Clinical Epigenetics
#524
of 1,257 outputs
Outputs of similar age
#102,527
of 298,447 outputs
Outputs of similar age from Clinical Epigenetics
#23
of 30 outputs
Altmetric has tracked 22,867,327 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 1,257 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one has gotten more attention than average, scoring higher than 56% 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 298,447 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 64% of its contemporaries.
We're also able to compare this research output to 30 others from the same source and published within six weeks on either side of this one. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.