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Selective mode of action of plumbagin through BRCA1 deficient breast cancer stem cells

Overview of attention for article published in BMC Cancer, May 2016
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Title
Selective mode of action of plumbagin through BRCA1 deficient breast cancer stem cells
Published in
BMC Cancer, May 2016
DOI 10.1186/s12885-016-2372-4
Pubmed ID
Authors

Veena Somasundaram, Sreelatha K Hemalatha, Krishnendu Pal, Sutapa Sinha, Asha S. Nair, Debabrata Mukhopadhyay, Priya Srinivas

Abstract

Studies over the past decade and half have identified cancer stem cells (CSCs) to be responsible for tumorigenesis, invasion, sustenance of metastatic disease, radio- and chemo-resistance and tumor relapse. Recent reports have described the plasticity of breast CSCs (BCSCs) to shift between the epithelial and mesenchymal phenotypes via Epithelial-Mesenchymal Transition (EMT) and Mesenchymal-Epithelial Transition (MET) states as the reason for their invasive capabilities. Additionally, BRCA1 has been found to be a mammary stem cell fate determinant. However, it is not clear what would be the best marker that can be used for identifying CSCs in BRCA1 mutated cancers. Also, anticancer agents that can reduce CSC population in a BRCA1 defective condition have not been addressed so far. Putative BCSCs were identified based on Hoechst exclusion, CD44(+)/24(-/low) expression and Aldehyde Dehydrogenase 1 (ALDH1) positivity using flow cytometry. The 'stemness' of the isolated ALDH1+ cells were analysed by immunofluorescence, western blotting for stem cell and EMT markers as well as in vitro mammosphere assays. Induction of Reactive Oxygen Species (ROS) by Plumbagin (PB) in BCSCs was assayed by Dichloro-dihydro-fluorescein diacetate (DCF-DA) staining. Ovarian cancer xenografts treated with PB were subjected to immunohistochemical analysis to study the ability of PB to target CSCs. We have confirmed that ALDH1 positivity is the best marker for the identification of BCSCs in BRCA1-defective breast cancer cell lines when compared to the CD marker profile and Side Population (SP) analysis. BRCA1 status was observed to be a determinant of the abundance of epithelial-like (ALDH1+) or mesenchymal-like (CD44(+)/24(-/low)) BCSCs, and the reconstitution of a full length, wild type BRCA1 in HCC1937 breast cancer cells possessing a mutated BRCA1, transforms them from 'stem-like' to more 'mesenchymal'. For the first time we have shown that Plumbagin (PB), a naturally occurring naphthoquinone which is predominantly a ROS inducer, could reduce BCSCs specifically in BRCA1-defective, basal-like cancer cells. The best marker for identifying BCSCs in BRCA1 defective condition could be ALDH1 and that BRCA1 mutated BCSCs would be mostly 'stem like' than 'mesenchymal'. Also ROS inducers like PB could reduce BCSCs in BRCA1 defective cancers.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 %
Australia 1 2%
Unknown 40 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 17%
Student > Bachelor 6 15%
Student > Doctoral Student 4 10%
Other 4 10%
Student > Master 4 10%
Other 8 20%
Unknown 8 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 24%
Medicine and Dentistry 10 24%
Agricultural and Biological Sciences 6 15%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Business, Management and Accounting 1 2%
Other 1 2%
Unknown 11 27%

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 03 June 2016.
All research outputs
#6,799,099
of 7,849,747 outputs
Outputs from BMC Cancer
#2,752
of 3,368 outputs
Outputs of similar age
#224,350
of 269,242 outputs
Outputs of similar age from BMC Cancer
#121
of 156 outputs
Altmetric has tracked 7,849,747 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 3,368 research outputs from this source. They receive a mean Attention Score of 3.4. 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 269,242 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 156 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.