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Pro-apoptotic and pro-autophagic effects of the Aurora kinase A inhibitor alisertib (MLN8237) on human osteosarcoma U-2 OS and MG-63 cells through the activation of mitochondria-mediated pathway and…

Overview of attention for article published in Drug Design, Development and Therapy, March 2015
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Title
Pro-apoptotic and pro-autophagic effects of the Aurora kinase A inhibitor alisertib (MLN8237) on human osteosarcoma U-2 OS and MG-63 cells through the activation of mitochondria-mediated pathway and inhibition of p38 MAPK/PI3K/Akt/mTOR signaling pathway
Published in
Drug Design, Development and Therapy, March 2015
DOI 10.2147/dddt.s74197
Pubmed ID
Authors

Shu-Feng Zhou, Ningkui Niu, Zi-Li Wang, Shuting Pan, Hui-Qiang Ding, Giang Au, Zhixue He, Zhi-Wei Zhou, Guozhi Xiao, Yin-Xue Yang, Xueji Zhang, Tianxin Yang, Xiao-Wu Chen, Jiaxuan Qiu

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor occurring mostly in children and adolescents between 10 and 20 years of age with poor response to current therapeutics. Alisertib (ALS, MLN8237) is a selective Aurora kinase A inhibitor that displays anticancer effects on several types of cancer. However, the role of ALS in the treatment of OS remains unknown. This study aimed to investigate the effects of ALS on the cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition (EMT) and the underlying mechanisms in two human OS cell lines U-2 OS and MG-63. The results showed that ALS had potent growth inhibitory, pro-apoptotic, pro-autophagic, and EMT inhibitory effects on U-2 OS and MG-63 cells. ALS remarkably induced G2/M arrest and down-regulated the expression levels of cyclin-dependent kinases 1 and 2 and cyclin B1 in both U-2 OS and MG-63 cells. ALS markedly induced mitochondria-mediated apoptosis with a significant increase in the expression of key pro-apoptotic proteins and a decrease in main anti-apoptotic proteins. Furthermore, ALS promoted autophagic cell death via the inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways, and activation of 5'-AMP-dependent kinase (AMPK) signaling pathway. Inducers or inhibitors of apoptosis or autophagy simultaneously altered ALS-induced apoptotic and autophagic death in both U-2 OS and MG-63 cells, suggesting a crosstalk between these two primary modes of programmed cell death. Moreover, ALS suppressed EMT-like phenotypes with a marked increase in the expression of E-cadherin but a decrease in N-cadherin in U-2 OS and MG-63 cells. ALS treatment also induced reactive oxygen species (ROS) generation but inhibited the expression levels of sirtuin 1 and nuclear factor-erythroid-2-related factor 2 (Nrf2) in both cell lines. Taken together, these findings show that ALS promotes apoptosis and autophagy but inhibits EMT via PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways with involvement of ROS- and sirtuin 1-associated pathways in U-2 OS and MG-63 cells. ALS is a promising anticancer agent in OS treatment and further studies are needed to confirm its efficacy and safety in OS chemotherapy.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
France 1 3%
Unknown 29 97%

Demographic breakdown

Readers by professional status Count As %
Student > Master 7 23%
Student > Bachelor 5 17%
Student > Ph. D. Student 4 13%
Student > Doctoral Student 3 10%
Lecturer > Senior Lecturer 2 7%
Other 8 27%
Unknown 1 3%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 30%
Agricultural and Biological Sciences 8 27%
Medicine and Dentistry 8 27%
Immunology and Microbiology 1 3%
Psychology 1 3%
Other 1 3%
Unknown 2 7%

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 21 March 2015.
All research outputs
#20,265,771
of 22,796,179 outputs
Outputs from Drug Design, Development and Therapy
#1,578
of 2,083 outputs
Outputs of similar age
#216,379
of 256,542 outputs
Outputs of similar age from Drug Design, Development and Therapy
#50
of 69 outputs
Altmetric has tracked 22,796,179 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 2,083 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 69 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.