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SHR Neuro Krebs Kardio Lipid

Wallner, M; Khafaga, M; Kolesnik, E; Vafiadis, A; Schwantzer, G; Eaton, DM; Curcic, P; Köstenberger, M; Knez, I; Rainer, PP; Pichler, M; Pieske, B; Lewinski, DV.
Istaroxime, a potential anticancer drug in prostate cancer, exerts beneficial functional effects in healthy and diseased human myocardium.
Oncotarget. 2017; 8(30):49264-49274 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Curcic Pero
Khafaga Mounir
Knez Igor
Kolesnik Ewald
Köstenberger Martin
Pichler Martin
Rainer Peter
Schwantzer Gerold
Vafiadis Aris Alexander
von Lewinski Dirk
Wallner Markus
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Number of Figures: 3
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Abstract:
The current gold standard for prostate cancer treatment is androgen deprivation therapy and antiandrogenic agents. However, adverse cardiovascular events including heart failure can limit therapeutic use. Istaroxime, which combines Na+-K+-ATPase (NKA) inhibition with sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) stimulation, has recently shown promising anti-neoplastic effects in prostate cancer (PC) models and may also improve cardiac function. Considering the promising anticancer effects of istaroxime, we aimed to assess its functional effects on human myocardium. Istaroxime and strophanthidin elicited dose-dependent positive inotropic effects with a decline in developed force at supraphysiological concentrations in human atrial, nonfailing, and failing ventricular (ToF) myocardium. Diastolic force and RT50% did not change after exposure to both drugs. The maximal developed force in our in-vitro model of heart failure (ToF) was significantly higher after istaroxime administration. Such a difference did not occur in atrial or nonfailing ventricular trabeculae and was not applicable to the diastolic force. Human atrial and ventricular trabeculae were isolated from nonfailing hearts and hearts of infants with tetralogy of Fallot (ToF), which were used as an in-vitro model of heart failure. The samples were electrically stimulated and treated with increasing concentrations of istaroxime and strophanthidin (10 nM-1 μM). Systolic and diastolic force development and relaxation parameters (RT50%) were analyzed. Combined NKA inhibition/SERCA2a stimulation increases contractility in atrial, nonfailing, and failing myocardium. Considering that heart failure is a potential side effect of current PC treatments, especially in elderly patients, istaroxime might combine beneficial cardiac and anti-cancer properties.

Find related publications in this database (Keywords)
prostate cancer
hormone therapy
cardiac disease models
heart failure
istaroxime
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