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Istaroxime Inhibits Motility and Down-Regulates Orai1 Expression, SOCE and FAK Phosphorylation in Prostate Cancer Cells

Overview of attention for article published in Cellular Physiology & Biochemistry, July 2017
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Title
Istaroxime Inhibits Motility and Down-Regulates Orai1 Expression, SOCE and FAK Phosphorylation in Prostate Cancer Cells
Published in
Cellular Physiology & Biochemistry, July 2017
DOI 10.1159/000479200
Pubmed ID
Authors

Matias Julian Stagno, Nefeli Zacharopoulou, Jonas Bochem, Anna Tsapara, Lisann Pelzl, Tamer al-Maghout, Galatea Kallergi, Saad Alkahtani, Konstantinos Alevizopoulos, Konstantinos Dimas, Theodora Calogeropoulou, Steven W. Warmann, Florian Lang, Evi Schmid, Christos Stournaras

Abstract

Istaroxime is a validated inotropic Na+/K+ ATPase inhibitor currently in development for the treatment of various cardiac conditions. Recent findings established that this steroidal drug exhibits potent apoptotic responses in prostate tumors in vitro and in vivo, by affecting key signaling orchestrating proliferation and apoptosis, such as c-Myc and caspase 3, Rho GTPases and actin cytoskeleton dynamics. In the present study we examined whether istaroxime is affecting cell motility and analyzed the underlying mechanism in prostate tumor cells. Migration was assessed by transwell and wound healing assays, Orai1 and Stim1 abundance by RT-PCR and confocal immunofluorescence microscopy, Fura-2 fluorescence was utilized to determine intracellular Ca2+ and Western blotting for FAK/pFAK measurements. We observed strong inhibition of cell migration in istaroxime treated DU-145 prostate cancer cells. Istaroxime further decreased Orai1 and Stim1 transcript levels and downregulated Orai1 protein expression. Moreover, SOCE was significantly decreased upon istaroxime treatment. Furthermore, istaroxime strikingly diminished phosphorylated FAK levels. Interestingly, the efficacy of istaroxime on the inhibition of DU-145 cell migration was further enhanced by blocking Orai1 with 2-APB and FAK with the specific inhibitor PF-00562271. These results provide strong evidence that istaroxime prevents cell migration and motility of DU-145 prostate tumor cells, an effect at least partially attributed to Orai1 downregulation and FAK de-activation. Collectively our results indicate that this enzyme inhibitor, besides its pro-apoptotic action, affects motility of cancer cells, supporting its potential role as a strong candidate for further clinical cancer drug development.

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Mendeley readers

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 %
Unknown 30 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 17%
Student > Bachelor 4 13%
Professor > Associate Professor 3 10%
Professor 2 7%
Researcher 2 7%
Other 6 20%
Unknown 8 27%
Readers by discipline Count As %
Medicine and Dentistry 8 27%
Agricultural and Biological Sciences 6 20%
Biochemistry, Genetics and Molecular Biology 3 10%
Immunology and Microbiology 1 3%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Other 0 0%
Unknown 11 37%
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 19 July 2017.
All research outputs
#20,970,494
of 25,756,911 outputs
Outputs from Cellular Physiology & Biochemistry
#1,322
of 2,454 outputs
Outputs of similar age
#252,146
of 325,684 outputs
Outputs of similar age from Cellular Physiology & Biochemistry
#58
of 103 outputs
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