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Targeting autophagy to modulate cell survival: a comparative analysis in cancer, normal and embryonic cells

Overview of attention for article published in Histochemistry and Cell Biology, June 2017
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Title
Targeting autophagy to modulate cell survival: a comparative analysis in cancer, normal and embryonic cells
Published in
Histochemistry and Cell Biology, June 2017
DOI 10.1007/s00418-017-1590-4
Pubmed ID
Authors

Aleksandra Divac Rankov, Mila Ljujić, Marija Petrić, Dragica Radojković, Milica Pešić, Jelena Dinić

Abstract

Autophagy is linked to multiple cancer-related signaling pathways, and represents a defense mechanism for cancer cells under therapeutic stress. The crosstalk between apoptosis and autophagy is essential for both tumorigenesis and embryonic development. We studied the influence of autophagy on cell survival in pro-apoptotic conditions induced by anticancer drugs in three model systems: human cancer cells (NCI-H460, COR-L23 and U87), human normal cells (HaCaT and MRC-5) and zebrafish embryos (Danio rerio). Autophagy induction with AZD2014 and tamoxifen antagonized the pro-apoptotic effect of chemotherapeutics doxorubicin and cisplatin in cell lines, while autophagy inhibition by wortmannin and chloroquine synergized the action of both anticancer agents. This effect was further verified by assessing cleaved caspase-3 and PARP-1 levels. Autophagy inhibitors significantly increased both apoptotic markers when applied in combination with doxorubicin while autophagy inducers had the opposite effect. In a similar manner, autophagy induction in zebrafish embryos prevented cisplatin-induced apoptosis in the tail region while autophagy inhibition increased cell death in the tail and retina of cisplatin-treated animals. Autophagy modulation with direct inhibitors of the PI3kinase/Akt/mTOR pathway (AZD2014 and wortmannin) triggered the cellular response to anticancer drugs more effectively in NCI-H460 and zebrafish embryonic models compared to HaCaT suggesting that these modulators are selective towards rapidly proliferating cells. Therefore, evaluating the autophagic properties of chemotherapeutics could help determine more accurately the fate of different cell types under treatment. Our study underlines the importance of testing autophagic activity of potential anticancer agents in a comparative approach to develop more rational anticancer therapeutic strategies.

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Mendeley readers

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 %
Researcher 6 21%
Student > Ph. D. Student 5 17%
Student > Bachelor 4 14%
Student > Master 4 14%
Professor > Associate Professor 2 7%
Other 5 17%
Unknown 3 10%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 38%
Agricultural and Biological Sciences 5 17%
Pharmacology, Toxicology and Pharmaceutical Science 4 14%
Neuroscience 2 7%
Social Sciences 1 3%
Other 2 7%
Unknown 4 14%
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 01 July 2017.
All research outputs
#21,697,638
of 24,217,893 outputs
Outputs from Histochemistry and Cell Biology
#774
of 926 outputs
Outputs of similar age
#279,477
of 318,855 outputs
Outputs of similar age from Histochemistry and Cell Biology
#6
of 6 outputs
Altmetric has tracked 24,217,893 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 926 research outputs from this source. They receive a mean Attention Score of 3.6. This one is in the 1st percentile – i.e., 1% 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 318,855 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 6 others from the same source and published within six weeks on either side of this one.