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Steroidal Cardiac Na+/K (+) ATPase Inhibitors Exhibit Strong Anti-Cancer Potential in vitro and in Prostate and Lung Cancer Xenografts in vivo
dc.creator | Dimas, K. | en |
dc.creator | Papadopoulou, N. | en |
dc.creator | Baskakis, C. | en |
dc.creator | Prousis, K. C. | en |
dc.creator | Tsakos, M. | en |
dc.creator | Alkahtani, S. | en |
dc.creator | Honisch, S. | en |
dc.creator | Lang, F. | en |
dc.creator | Calogeropoulou, T. | en |
dc.creator | Alevizopoulos, K. | en |
dc.creator | Stournaras, C. | en |
dc.date.accessioned | 2015-11-23T10:25:30Z | |
dc.date.available | 2015-11-23T10:25:30Z | |
dc.date.issued | 2014 | |
dc.identifier.issn | 1871-5206 | |
dc.identifier.uri | http://hdl.handle.net/11615/27054 | |
dc.description.abstract | 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 GI(50), 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. | en |
dc.source | Anti-Cancer Agents in Medicinal Chemistry | en |
dc.source.uri | <Go to ISI>://WOS:000335390800014 | |
dc.subject | Na+/K+ ATPase | en |
dc.subject | steroidal cardiac inhibitors | en |
dc.subject | multi-drug resistant cells | en |
dc.subject | lung tumors | en |
dc.subject | prostate tumors | en |
dc.subject | NA,K-ATPASE BETA-SUBUNIT | en |
dc.subject | SODIUM-PUMP | en |
dc.subject | CARDIOTONIC STEROIDS | en |
dc.subject | EPITHELIAL-CELLS | en |
dc.subject | TUMOR-GROWTH | en |
dc.subject | NA/K-ATPASE | en |
dc.subject | DRUG | en |
dc.subject | EXPRESSION | en |
dc.subject | GLYCOSIDES | en |
dc.subject | NA+,K+-ATPASE | en |
dc.subject | Oncology | en |
dc.subject | Chemistry, Medicinal | en |
dc.title | Steroidal Cardiac Na+/K (+) ATPase Inhibitors Exhibit Strong Anti-Cancer Potential in vitro and in Prostate and Lung Cancer Xenografts in vivo | en |
dc.type | journalArticle | en |
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