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Tideglusib induces apoptosis in human neuroblastoma IMR32 cells, provoking sub-G0/G1 accumulation and ROS generation

Overview of attention for article published in Environmental Toxicology & Pharmacology, July 2016
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Title
Tideglusib induces apoptosis in human neuroblastoma IMR32 cells, provoking sub-G0/G1 accumulation and ROS generation
Published in
Environmental Toxicology & Pharmacology, July 2016
DOI 10.1016/j.etap.2016.07.013
Pubmed ID
Authors

Theodore Lemuel Mathuram, Vilwanathan Ravikumar, Lisa M. Reece, Selvaraju Karthik, Changam Sheela Sasikumar, Kotturathu Mammen Cherian

Abstract

Neuroblastoma is the most common tumor amongst children amounting to nearly 15% of cancer deaths. This cancer is peculiar in its characteristics, exhibiting differentiation, maturation and metastatic transformation leading to poor prognosis and low survival rates among children. Chemotherapy, though toxic to normal cells, has shown to improve the survival of the patient with emphasis given more towards targeting angiogenesis. Recently, Tideglusib was designed as an 'Orphan Drug' to target the neurodegenerative Alzheimer's disease and gained significant momentum in its function during clinical trials. Duffy et al. recently reported a reduction in cell viability of human IMR32 neuroblastoma cells when treated with Tideglusib at varying concentrations. We investigated the effects of Tideglusib, at various concentrations, compared to Lithium chloride at various concentrations, on IMR32 cells. Lithium, a known GSK-3 inhibitor, was used as a standard to compare the efficiency of Tideglusib in a dose-dependent manner. Cell viability was assessed by MTT assay. The stages of apoptosis were evaluated by AO/EB staining and nuclear damage was determined by Hoechst 33258 staining. Reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were assessed by DCFDA dye and Rhodamine-123 dye, respectively. Tideglusib reported a significant dose-dependent increase in pro-apoptotic proteins (PARP, Caspase-9, Caspase-7, Caspase-3) and tumor-related genes (FasL, TNF-α, Cox-2, IL-8, Caspase-3). Anti-GSK3 β, pGSK3 β, Bcl-2, Akt-1, p-Akt1 protein levels were observed with cells exposed to Tideglusib and Lithium chloride. No significant dose-dependent changes were observed for the mRNA expression of collagenase MMP-2, the tumor suppressor p53, or the cell cycle protein p21. Our study also reports Tideglusib reducing colony formation and increasing the level of sub-G0/G1 population in IMR32 cells. Our investigations report the significance of Tideglusib as a promising apoptotic inducer in human neuroblastoma IMR32 cells. Our study also reports that LiCl reduced cell viability in IMR32 cells inducing apoptosis mediated by ROS generation.

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

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 22%
Student > Master 6 13%
Researcher 5 11%
Student > Bachelor 5 11%
Student > Doctoral Student 3 7%
Other 6 13%
Unknown 10 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 24%
Medicine and Dentistry 6 13%
Chemistry 5 11%
Pharmacology, Toxicology and Pharmaceutical Science 3 7%
Agricultural and Biological Sciences 2 4%
Other 5 11%
Unknown 13 29%
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 05 August 2016.
All research outputs
#20,655,488
of 25,373,627 outputs
Outputs from Environmental Toxicology & Pharmacology
#809
of 1,189 outputs
Outputs of similar age
#295,388
of 377,881 outputs
Outputs of similar age from Environmental Toxicology & Pharmacology
#15
of 27 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,189 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one is in the 18th percentile – i.e., 18% 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 377,881 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 11th percentile – i.e., 11% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 27 others from the same source and published within six weeks on either side of this one. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.