↓ Skip to main content

Novel smac mimetic APG-1387 elicits ovarian cancer cell killing through TNF-alpha, Ripoptosome and autophagy mediated cell death pathway

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, March 2018
Altmetric Badge

About this Attention Score

  • Average Attention Score compared to outputs of the same age and source

Mentioned by

twitter
2 X users

Readers on

mendeley
19 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Novel smac mimetic APG-1387 elicits ovarian cancer cell killing through TNF-alpha, Ripoptosome and autophagy mediated cell death pathway
Published in
Journal of Experimental & Clinical Cancer Research, March 2018
DOI 10.1186/s13046-018-0703-9
Pubmed ID
Authors

Bao-Xia Li, Heng-Bang Wang, Miao-Zhen Qiu, Qiu-Yun Luo, Han-Jie Yi, Xiang-Lei Yan, Wen-Tao Pan, Lu-Ping Yuan, Yu-Xin Zhang, Jian-Hua Xu, Lin Zhang, Da-Jun Yang

Abstract

Ovarian cancer is a deadly disease. Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are frequently dysregulated in ovarian cancer. Overexpression of IAPs proteins has been correlated with tumorigenesis, treatment resistance and poor prognosis. Reinstalling functional cell death machinery by pharmacological inhibition of IAPs proteins may represent an attractive therapeutic strategy for treatment of ovarian cancer. CCK-8 and colony formation assay was performed to examine cytotoxic activity. Apoptosis was analyzed by fluorescence microscopy, flow cytometry and TUNEL assay. Elisa assay was used to determine TNFα protein. Caspase activity assay was used for caspase activation evaluation. Immunoprecipitation and siRNA interference were carried out for functional analysis. Western blotting analysis were carried out to test protein expression. Ovarian cancer cell xenograft nude mice model was used for in vivo efficacy evaluation. APG-1387 demonstrated potent inhibitory effect on ovarian cancer cell growth and clonogenic cell survival. APG-1387 induced RIP1- and TNFα-dependent apoptotic cell death in ovarian cancer through downregulation of IAPs proteins and induction of caspase-8/FADD/RIP1 complex, which drives caspase-8 activation. NF-κB signaling pathway was activated upon APG-1387 treatment and RIP1 contributed to NF-κB activation. APG-1387 induced cytoprotective autophagy while triggering apoptosis in ovarian cancer cells and inhibition of autophagy enhanced APG-1387-induced apoptotic cell death. APG-1387 exhibited potent antitumor activity against established human ovarian cancer xenografts. Our results demonstrate that APG-1387 targets IAPs proteins to potently elicit apoptotic cell death in vitro and in vivo, and provide mechanistic and applicable rationale for future clinical evaluation of APG-1387 in ovarian cancer.

X Demographics

X Demographics

The data shown below were collected from the profiles of 2 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 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 26%
Student > Bachelor 4 21%
Student > Ph. D. Student 2 11%
Student > Master 2 11%
Student > Postgraduate 1 5%
Other 0 0%
Unknown 5 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 42%
Agricultural and Biological Sciences 2 11%
Pharmacology, Toxicology and Pharmaceutical Science 1 5%
Immunology and Microbiology 1 5%
Social Sciences 1 5%
Other 1 5%
Unknown 5 26%
Attention Score in Context

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 14 March 2018.
All research outputs
#17,292,294
of 25,382,440 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#1,247
of 2,380 outputs
Outputs of similar age
#226,541
of 350,479 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#26
of 39 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,380 research outputs from this source. They receive a mean Attention Score of 4.8. This one is in the 38th percentile – i.e., 38% 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 350,479 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 39 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.