Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Steroidal cardiac Na+/K+ ATPase inhibitors exhibit strong anti-cancer potential in vitro and in prostate and lung cancer xenografts in vivo
Δημιουργός/Συγγραφέας:	Dimas K. Papadopoulou N. Baskakis C. [EL] Προύσης, Κυριάκος[EN] Prousis, Kyriakos Tsakos M. Alkahtani S. Honisch S. Lang F. [EL] Καλογεροπούλου, Θεοδώρα[EN] Calogeropoulou, Theodora Alevizopoulos K. Stournaras C.
Εκδότης:	Bentham Science Publishers B.V.
Ημερομηνία:	2014
Γλώσσα:	Αγγλικά
ISSN:	1871-5206
DOI:	10.2174/18715206113136660338
Άλλο:	PubMed ID: 24066843
Περίληψη:	Sodium potassium pump (Na+/K+ ATPase) is a validated pharmacological target for the treatment of congestive heart failure. Recent data with inotropic drugs such as digoxin & digitoxin (digitalis) suggest a potent anti-cancer action of these drugs and promote Na+/K+ ATPase as a novel therapeutic target in cancer. However, digitalis have narrow therapeutic indices, are pro-arrhythmic and are considered non-developable drugs by the pharmaceutical industry. On the contrary, a series of recently-developed steroidal inhibitors showed better pharmacological properties and clinical activities in cardiac patients. Their anti-cancer activity however, remained unknown. In this study, we synthesized seventeen steroidal cardiac inhibitors and explored for the first time their anti-cancer activity in vitro and in vivo. Our results indicate potent anti-cancer actions of steroidal cardiac inhibitors in multiple cell lines from different tumor panels including multi-drug resistant cells. Furthermore, the most potent compound identified in our studies, the 3-[(R)-3-pyrrolidinyl]oxime derivative 3, showed outstanding potencies (as measured by GI50, TGI and LC50 values) in most cells in vitro, was selectively cytotoxic in cancer versus normal cells showing a therapeutic index of 31.7 and exhibited significant tumor growth inhibition in prostate and lung xenografts in vivo. Collectively, our results suggest that previously described cardiac Na+/K+ ATPase inhibitors have potent anti-cancer actions and may thus constitute strong re-purposing candidates for further cancer drug development.
Τίτλος πηγής δημοσίευσης:	Anti-Cancer Agents in Medicinal Chemistry
Τόμος/Κεφάλαιο:	14
Τεύχος:	5
Σελίδες:	762-770
Θεματική Κατηγορία:	[EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	Lung tumors Multi-drug resistant cells Prostate tumors Steroidal cardiac inhibitors
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2014 Bentham Science Publishers.
Σημειώσεις:	GRK 1302, SFB773
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο