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Arctigenin Inhibits Liver Cancer Tumorigenesis by Inhibiting Gankyrin Expression via C/EBPα and PPARα

Overview of attention for article published in Frontiers in Pharmacology, March 2018
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Title
Arctigenin Inhibits Liver Cancer Tumorigenesis by Inhibiting Gankyrin Expression via C/EBPα and PPARα
Published in
Frontiers in Pharmacology, March 2018
DOI 10.3389/fphar.2018.00268
Pubmed ID
Authors

Ying Sun, Yu-jun Tan, Zhan-zhao Lu, Bing-bing Li, Cheng-hong Sun, Tao Li, Li-li Zhao, Zhong Liu, Gui-min Zhang, Jing-chun Yao, Jie Li

Abstract

Burdock (Arctium lappa) is a popular vegetable in China and Japan that is consumed for its general health benefits. The principal active component of burdock is arctigenin, which shows a range of bioactivities in vivo and in vitro. Here, we investigated the potential anti-tumor effects of arctigenin using two human hepatocellular carcinoma (HCC) cell lines, HepG2 and Hep3B, and sought to elucidate its potential mechanisms of action. Our results showed that arctigenin treatment inhibited cell growth in both HepG2 and Hep3B cell lines (IC50 of 4.74 nM for HepG2 cells, and of 59.27 nM for Hep3B cells). In addition, migration, invasion, and colony formation by HepG2 cells were significantly inhibited by arctigenin. By contrast, treatment of Hep3B cells with arctigenin did not alter these parameters. Arctigenin also significantly reduced the levels of gankyrin mRNA and protein in HepG2 cells, but not in Hep3B cells. A luciferase assay indicated that arctigenin targeted the -450 to -400 region of the gankyrin promoter. This region is also the potential binding site for both C/EBPα and PPARα, as predicted and confirmed by an online software analysis and ChIP assay. Additionally, a co-immunoprecipitation (Co-IP) assay showed that binding between C/EBPα and PPARα was increased in the presence of arctigenin. However, arctigenin did not increase the expression of C/EBPα or PPARα protein. A binding screening assay and liquid chromatography-mass spectrometry (LC-MS) were performed to identify the mechanisms by which arctigenin regulates gankyrin expression. The results suggested that arctigenin could directly increase C/EBPα binding to the gankyrin promoter (-432 to -422 region), but did not affect PPARα binding. Expression of gankyrin, C/EBPα, and PPARα were analyzed in tumor tissues of patients using real-time PCR. Both C/EBPα and PPARα showed negative correlations with gankyrin. In tumor-bearing mice, arctigenin had a significant inhibitory effect on HCC growth. In conclusion, our results suggested that arctigenin could inhibit liver cancer growth by directly recruiting C/EBPα to the gankyrin promoter. PPARα subsequently bound to C/EBPα, and both had a negative regulatory effect on gankyrin expression. This study has identified a new mechanism of action of arctigenin against liver cancer growth.

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X Demographics

The data shown below were collected from the profiles of 5 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 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 %
Researcher 4 13%
Other 3 10%
Student > Ph. D. Student 3 10%
Student > Bachelor 2 6%
Professor > Associate Professor 2 6%
Other 5 16%
Unknown 12 39%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 19%
Pharmacology, Toxicology and Pharmaceutical Science 3 10%
Agricultural and Biological Sciences 3 10%
Medicine and Dentistry 3 10%
Chemistry 2 6%
Other 2 6%
Unknown 12 39%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 15 June 2023.
All research outputs
#13,940,461
of 23,867,274 outputs
Outputs from Frontiers in Pharmacology
#4,167
of 17,714 outputs
Outputs of similar age
#169,109
of 333,222 outputs
Outputs of similar age from Frontiers in Pharmacology
#102
of 375 outputs
Altmetric has tracked 23,867,274 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 17,714 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has done well, scoring higher than 75% 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 333,222 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 375 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 72% of its contemporaries.