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Cooperative antitumor activities of carnosic acid and Trastuzumab in ERBB2+ breast cancer cells

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, November 2017
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2 tweeters

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41 Mendeley
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Title
Cooperative antitumor activities of carnosic acid and Trastuzumab in ERBB2+ breast cancer cells
Published in
Journal of Experimental & Clinical Cancer Research, November 2017
DOI 10.1186/s13046-017-0615-0
Pubmed ID
Authors

Carolina D’Alesio, Grazia Bellese, Maria Cristina Gagliani, Cinzia Aiello, Elena Grasselli, Gianluca Marcocci, Angela Bisio, Sara Tavella, Tiziana Daniele, Katia Cortese, Patrizio Castagnola

Abstract

ERBB2 is overexpressed in up to 20-30% of human breast cancers (BCs), and it is associated with aggressive disease. Trastuzumab (Tz), a humanized monoclonal antibody, improves the prognosis associated with ERBB2-amplified BCs. However, the development of resistance remains a significant challenge. Carnosic acid (CA) is a diterpene found in rosemary and sage, endowed with anticancer properties. In this in vitro study, we have investigated whether Tz and CA have cooperative effects on cell survival of ERBB2 overexpressing (ERBB2(+)) cells and whether CA might restore Tz sensitivity in Tz-resistant cells. We have studied BC cell migration and survival upon CA and Tz treatment. In particular, migration ability was assessed by transwell assay while cell survival was assessed by MTT assay. In addition, we have performed cell cycle and apoptosis analysis by high-resolution DNA flow cytometry and annexin-V, resazurin and sytox blue staining by flow cytometry, respectively. The expression of proteins involved in cell cycle progression, ERBB2 signaling pathway, and autophagy was evaluated by immunoblot and immunofluorescence analysis. Cellular structures relevant to the endosome/lysosome and autophagy pathways have been studied by immunofluorescence and transmission electron microscopy. We report that, in ERBB2(+) BC cells, CA reversibly enhances Tz inhibition of cell survival, cooperatively inhibits cell migration and induces cell cycle arrest in G0/G1. These events are accompanied by ERBB2 down-regulation, deregulation of the PI3K/AKT/mTOR signaling pathway and up-regulation of both CDKN1A/p21(WAF1) and CDKN1B/p27(KIP1). Furthermore, we have demonstrated that CA impairs late autophagy and causes derangement of the lysosomal compartment as shown by up-regulation of SQSTM1/p62 and ultrastructural analysis. Accordingly, we have found that CA restores, at least in part, sensitivity to Tz in SKBR-3 Tz-resistant cell line. Our data demonstrate the cooperation between CA and Tz in inhibiting cell migration and survival of ERBB2(+) BC cells that warrant further studies to establish if CA or CA derivatives may be useful in vivo in the treatment of ERBB2(+) cancers.

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

Geographical breakdown

Country Count As %
Unknown 41 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 17%
Student > Master 5 12%
Student > Ph. D. Student 4 10%
Student > Bachelor 4 10%
Student > Doctoral Student 3 7%
Other 8 20%
Unknown 10 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 24%
Pharmacology, Toxicology and Pharmaceutical Science 7 17%
Agricultural and Biological Sciences 3 7%
Immunology and Microbiology 2 5%
Medicine and Dentistry 2 5%
Other 5 12%
Unknown 12 29%

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 20 July 2018.
All research outputs
#14,181,497
of 17,762,776 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#802
of 1,482 outputs
Outputs of similar age
#245,865
of 330,893 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#58
of 112 outputs
Altmetric has tracked 17,762,776 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,482 research outputs from this source. They receive a mean Attention Score of 2.6. This one is in the 28th percentile – i.e., 28% 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 330,893 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 112 others from the same source and published within six weeks on either side of this one. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.