Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Istaroxime Inhibits Motility and Down-Regulates Orai1 Expression, SOCE and FAK Phosphorylation in Prostate Cancer Cells
Δημιουργός/Συγγραφέας:	Stagno M.J. Zacharopoulou N. Bochem J. Tsapara A. Pelzl L. Al-Maghout T. Kallergi G. Alkahtani S. Alevizopoulos K. Dimas K. [EL] Καλογεροπούλου, Θεοδώρα[EN] Calogeropoulou, Theodora Warmann S.W. Lang F. Schmid E. Stournaras C.
Εκδότης:	S. Karger AG
Ημερομηνία:	2017
Γλώσσα:	Αγγλικά
ISSN:	1015-8987
DOI:	10.1159/000479200
Άλλο:	PubMed ID: 28704809
Περίληψη:	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.
Τίτλος πηγής δημοσίευσης:	Cellular Physiology and Biochemistry
Τόμος/Κεφάλαιο:	42
Τεύχος:	4
Σελίδες:	1366-1376
Θεματική Κατηγορία:	[EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	DU-145 prostate cancer cells FAK Istaroxime Migration Orai1 SOCE
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2017 The Author(s). Published by S. Karger AG, Basel.
Όροι και προϋποθέσεις δικαιωμάτων:	All Open Access, Gold
Σημειώσεις:	009; Deutsche Forschungsgemeinschaft, DFG; King Saud University, KSU. This study was supported by the International Scientific Partnership Program ISPP at King Saud University (KSU-ISPP#009), the Deutsche Forschungsgemeinschaft (Mercator Professorship Program) and the Open Access Publishing Fund of Tuebingen University.
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο