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Discovery and characterization of Isofistularin-3, a marine brominated alkaloid, as a new DNA demethylating agent inducing cell cycle arrest and sensitization to TRAIL in cancer cells

Overview of attention for article published in Oncotarget, March 2016
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2 tweeters

Citations

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24 Dimensions

Readers on

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29 Mendeley
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Title
Discovery and characterization of Isofistularin-3, a marine brominated alkaloid, as a new DNA demethylating agent inducing cell cycle arrest and sensitization to TRAIL in cancer cells
Published in
Oncotarget, March 2016
DOI 10.18632/oncotarget.8210
Pubmed ID
Authors

Cristina Florean, Michael Schnekenburger, Jin-Young Lee, Kyung Rok Kim, Aloran Mazumder, Sungmi Song, Jae-Myun Kim, Cindy Grandjenette, Jeoung-Gyun Kim, Ah-Young Yoon, Mario Dicato, Kyu-Won Kim, Christo Christov, Byung-Woo Han, Peter Proksch, Marc Diederich

Abstract

We characterized the brominated alkaloid Isofistularin-3 (Iso-3), from the marine sponge Aplysina aerophoba, as a new DNA methyltransferase (DNMT)1 inhibitor. Docking analysis confirmed our in vitro DNMT inhibition data and revealed binding of Iso-3 within the DNA binding site of DNMT1. Subsequent increased expression of tumor suppressor gene aryl hydrocarbon receptor (AHR) could be correlated to decreased methylation of CpG sites within the essential Sp1 regulatory region of its promoter. Iso-3 induced growth arrest of cancer cells in G0/G1 concomitant with increased p21 and p27 expression and reduced cyclin E1, PCNA and c-myc levels. Reduced proliferation was accompanied by morphological changes typical of autophagy revealed by fluorescent and transmission electron microscopy and validated by LC3I-II conversion. Furthermore, Iso-3 strongly synergized with tumor-necrosis-factor related apoptosis inducing ligand (TRAIL) in RAJI [combination index (CI) = 0.22] and U-937 cells (CI = 0.21) and increased TRAIL-induced apoptosis via a mechanism involving reduction of survivin expression but not of Bcl-2 family proteins nor X-linked inhibitor of apoptosis protein (XIAP). Iso-3 treatment decreased FLIPL expression and triggered activation of endoplasmatic reticulum (ER) stress with increased GRP78 expression, eventually inducing TRAIL receptor death receptor (DR)5 surface expression. Importantly, as a potential candidate for further anticancer drug development, Iso-3 reduced the viability, colony and in vivo tumor forming potential without affecting the viability of PBMCs from healthy donors or zebrafish development.

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 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 21%
Student > Bachelor 4 14%
Student > Master 4 14%
Researcher 3 10%
Other 2 7%
Other 7 24%
Unknown 3 10%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 31%
Pharmacology, Toxicology and Pharmaceutical Science 4 14%
Agricultural and Biological Sciences 3 10%
Chemistry 3 10%
Medicine and Dentistry 2 7%
Other 1 3%
Unknown 7 24%

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 24 February 2018.
All research outputs
#8,308,707
of 13,789,144 outputs
Outputs from Oncotarget
#3,335
of 12,270 outputs
Outputs of similar age
#133,928
of 264,318 outputs
Outputs of similar age from Oncotarget
#144
of 459 outputs
Altmetric has tracked 13,789,144 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,270 research outputs from this source. They receive a mean Attention Score of 3.8. This one has gotten more attention than average, scoring higher than 67% 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 264,318 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 459 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 64% of its contemporaries.