Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.18632/oncotarget.17540
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- Führende Autor*innen der Med Uni Graz
- Khafaga Mounir
- Kolesnik Ewald
- Wallner Markus
- Co-Autor*innen der Med Uni Graz
- Curcic Pero
- Knez Igor
- Koestenberger Martin
- Pichler Martin
- Pieske Burkert Mathias
- Rainer Peter
- Schwantzer Gerold
- VAFIADIS Aris Alexander
- von Lewinski Dirk
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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 (using NLM MeSH Indexing)
- Antineoplastic Agents - pharmacology
- Cardiotonic Agents - pharmacology
- Dose-Response Relationship, Drug -
- Etiocholanolone - analogs & derivatives
- Etiocholanolone - pharmacology
- Heart - drug effects
- Heart Atria - drug effects
- Heart Atria - metabolism
- Heart Failure - drug therapy
- Heart Failure - etiology
- Heart Failure - metabolism
- Heart Ventricles - drug effects
- Heart Ventricles - metabolism
- Humans -
- Strophanthidin - pharmacology
- Find related publications in this database (Keywords)
- prostate cancer
- hormone therapy
- cardiac disease models
- heart failure
- istaroxime