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Ascorbic acid and ascorbate-2-phosphate decrease HIF activity and malignant properties of human melanoma cells

Overview of attention for article published in BMC Cancer, November 2015
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Mentioned by

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3 tweeters

Citations

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22 Dimensions

Readers on

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56 Mendeley
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Title
Ascorbic acid and ascorbate-2-phosphate decrease HIF activity and malignant properties of human melanoma cells
Published in
BMC Cancer, November 2015
DOI 10.1186/s12885-015-1878-5
Pubmed ID
Authors

Sarah L. Miles, Adam P. Fischer, Sandeep J. Joshi, Richard M. Niles

Abstract

Hypoxia inducible factor-1 alpha (HIF-1α) is thought to play a role in melanoma carcinogenesis. Posttranslational regulation of HIF-1α is dependent on Prolyl hydroxylase (PHD 1-3) and Factor Inhibiting HIF (FIH) hydroxylase enzymes, which require ascorbic acid as a co-factor for optimal function. Depleted intra-tumoral ascorbic acid may thus play a role in the loss of HIF-1α regulation in melanoma. These studies assess the ability of ascorbic acid to reduce HIF-1α protein and transcriptional activity in metastatic melanoma and reduce its invasive potential. HIF-1α protein was evaluated by western blot, while transcriptional activity was measured by HIF-1 HRE-luciferase reporter gene activity. Melanoma cells were treated with ascorbic acid (AA) and ascorbate 2-phosphate (A2P) to assess their ability to reduce HIF-1α accumulation and activity. siRNA was used to deplete cellular PHD2 in order to evaluate this effect on AA's ability to lower HIF-1α levels. A2P's effect on invasive activity was measured by the Matrigel invasion assay. Data was analyzed by One-way ANOVA with Tukey's multiple comparisons test, or Student-T test as appropriate, with p < .05 considered significant. Supplementation with both AA and A2P antagonized normoxic as well as cobalt chloride- and PHD inhibitor ethyl 3, 4-dihydroxybenzoate induced HIF-1α protein stabilization and transcriptional activity. Knockdown of the PHD2 isoform with siRNA did not impede the ability of AA to reduce normoxic HIF-1α protein. Additionally, reducing HIF-1α levels with A2P resulted in a significant reduction in the ability of the melanoma cells to invade through Matrigel. These studies suggest a positive role for AA in regulating HIF-1α in melanoma by demonstrating that supplementation with either AA, or its oxidation-resistant analog A2P, effectively reduces HIF-1α protein and transcriptional activity in metastatic melanoma cells. Our data, while supporting the function of AA as a necessary cofactor for PHD and likely FIH activity, also suggests a potential non-PHD/FIH role for AA in HIF-1α regulation by its continued ability to reduce HIF-1α in the presence of PHD inhibition. The use of the oxidation-resistant AA analog, A2P, to reduce the ability of HIF-1α to promote malignant progression in melanoma cells and enhance their response to therapy warrants further investigation.

Twitter Demographics

The data shown below were collected from the profiles of 3 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 56 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Portugal 1 2%
Sweden 1 2%
Unknown 54 96%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 10 18%
Student > Master 8 14%
Student > Ph. D. Student 7 13%
Researcher 6 11%
Professor > Associate Professor 4 7%
Other 9 16%
Unknown 12 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 27%
Medicine and Dentistry 12 21%
Agricultural and Biological Sciences 9 16%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Computer Science 1 2%
Other 5 9%
Unknown 12 21%

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 January 2017.
All research outputs
#4,852,143
of 8,953,020 outputs
Outputs from BMC Cancer
#1,637
of 3,687 outputs
Outputs of similar age
#130,373
of 249,345 outputs
Outputs of similar age from BMC Cancer
#110
of 313 outputs
Altmetric has tracked 8,953,020 research outputs across all sources so far. This one is in the 27th percentile – i.e., 27% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,687 research outputs from this source. They receive a mean Attention Score of 3.8. This one is in the 44th percentile – i.e., 44% of its peers scored the same or lower than it.
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 249,345 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 313 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 56% of its contemporaries.