dc.creator | Stagno M.J., Zacharopoulou N., Bochem J., Tsapara A., Pelzl L., Al-Maghout T., Kallergi G., Alkahtani S., Alevizopoulos K., Dimas K., Calogeropoulou T., Warmann S.W., Lang F., Schmid E., Stournaras C. | en |
dc.date.accessioned | 2023-01-31T10:01:46Z | |
dc.date.available | 2023-01-31T10:01:46Z | |
dc.date.issued | 2017 | |
dc.identifier | 10.1159/000479200 | |
dc.identifier.issn | 10158987 | |
dc.identifier.uri | http://hdl.handle.net/11615/79355 | |
dc.description.abstract | Background/Aims: 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. Methods: 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 Ca 2+ and Western blotting for FAK/pFAK measurements. Results: 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. Conclusion: 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. © 2017 The Author(s). Published by S. Karger AG, Basel. | en |
dc.language.iso | en | en |
dc.source | Cellular Physiology and Biochemistry | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85025441168&doi=10.1159%2f000479200&partnerID=40&md5=2e3868869443214dfa50af2c760f0dcb | |
dc.subject | calcium ion | en |
dc.subject | calcium release activated calcium channel 1 | en |
dc.subject | focal adhesion kinase | en |
dc.subject | istaroxime | en |
dc.subject | pf 562271 | en |
dc.subject | phosphoprotein | en |
dc.subject | stromal interaction molecule 1 | en |
dc.subject | calcium | en |
dc.subject | calcium channel | en |
dc.subject | calcium release activated calcium channel 1 | en |
dc.subject | etiocholanolone | en |
dc.subject | fluorescent dye | en |
dc.subject | focal adhesion kinase 1 | en |
dc.subject | fura 2 | en |
dc.subject | istaroxime | en |
dc.subject | ORAI1 protein, human | en |
dc.subject | PF-00562271 | en |
dc.subject | protein kinase inhibitor | en |
dc.subject | PTK2 protein, human | en |
dc.subject | pyrimidine derivative | en |
dc.subject | sodium channel blocking agent | en |
dc.subject | STIM1 protein, human | en |
dc.subject | stromal interaction molecule 1 | en |
dc.subject | sulfonamide | en |
dc.subject | tumor protein | en |
dc.subject | antineoplastic activity | en |
dc.subject | Article | en |
dc.subject | cancer inhibition | en |
dc.subject | cell migration | en |
dc.subject | cell motility | en |
dc.subject | controlled study | en |
dc.subject | down regulation | en |
dc.subject | DU145 cell line | en |
dc.subject | enzyme phosphorylation | en |
dc.subject | priority journal | en |
dc.subject | prostate cancer cell line | en |
dc.subject | protein expression | en |
dc.subject | store operated calcium entry | en |
dc.subject | analogs and derivatives | en |
dc.subject | antagonists and inhibitors | en |
dc.subject | cell motion | en |
dc.subject | chemistry | en |
dc.subject | drug effects | en |
dc.subject | epithelium cell | en |
dc.subject | gene expression regulation | en |
dc.subject | genetics | en |
dc.subject | human | en |
dc.subject | male | en |
dc.subject | metabolism | en |
dc.subject | pathology | en |
dc.subject | phosphorylation | en |
dc.subject | prostate | en |
dc.subject | signal transduction | en |
dc.subject | tumor cell line | en |
dc.subject | Calcium | en |
dc.subject | Calcium Channels | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Cell Movement | en |
dc.subject | Epithelial Cells | en |
dc.subject | Etiocholanolone | en |
dc.subject | Fluorescent Dyes | en |
dc.subject | Focal Adhesion Kinase 1 | en |
dc.subject | Fura-2 | en |
dc.subject | Gene Expression Regulation, Neoplastic | en |
dc.subject | Humans | en |
dc.subject | Male | en |
dc.subject | Neoplasm Proteins | en |
dc.subject | ORAI1 Protein | en |
dc.subject | Phosphorylation | en |
dc.subject | Prostate | en |
dc.subject | Protein Kinase Inhibitors | en |
dc.subject | Pyrimidines | en |
dc.subject | Signal Transduction | en |
dc.subject | Sodium Channel Blockers | en |
dc.subject | Stromal Interaction Molecule 1 | en |
dc.subject | Sulfonamides | en |
dc.subject | S. Karger AG | en |
dc.title | Istaroxime Inhibits Motility and Down-Regulates Orai1 Expression, SOCE and FAK Phosphorylation in Prostate Cancer Cells | en |
dc.type | journalArticle | en |