Search results for "Cardiac glycoside"
showing 10 items of 11 documents
Cardiac Glycoside Glucoevatromonoside Induces Cancer Type-Specific Cell Death.
2018
Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC) and high-affinity binding to the Na+/K+-ATPase α subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission el…
The effect of cathartic agents on transmucosal electrical potential difference in the human rectum.
1980
Active ion transport in the colon is generating a transmucosal electrical potential difference (PD) of about 40 mV. Cathartic agents inhibit electrolyte and water net-absorption or cause net-secretion which should be reflected in a change of PD. In 83 normal subjects the effect of an isotonic eletrolyte solution (control) and different cathartic agents on rectal PD was tested: Laxatives (bisacodyl, rhein), bile acids (cholic and deoxycholic acid), fatty acids (oleic and ricinoleic acid) and cardiac glycosides (meproscillarin, digitoxin, digoxin). Bisacodyl, deoxycholic acid in high concentration, meproscillarin and digitoxin significantly decreased PD, while the other substances did not. Ca…
Identification of new P-glycoprotein inhibitors derived from cardiotonic steroids
2014
P-glycoprotein (ABCB1, MDR1) is capable of extruding chemotherapeutics outside the cell and its overexpression in certain cancer cells may cause failure of chemotherapy. Many attempts were carried out to identify potent inhibitors of this transporter and numerous compounds were shown to exert inhibitory effects in vitro, but so far none were able to make their way to the clinic due to serious complications. Natural compounds represent a great source of therapeutics, which are believed to be safe and effective. Therefore, we have screened a large library of naturally occurring cardiotonic steroids and their derivatives using high throughput flow cytometry. We were able to identify six compou…
Cytotoxicity of cardiotonic steroids in sensitive and multidrug-resistant leukemia cells and the link with Na(+)/K(+)-ATPase.
2015
Cardiotonic steroids have long been in clinical use for treatment of heart failure and are now emerging as promising agents in various diseases, especially cancer. Their main target is Na(+)/K(+)-ATPase, a membrane protein involved in cellular ion homeostasis. Na(+)/K(+)-ATPase has been implicated in cancer biology by affecting several cellular events and signaling pathways in both sensitive and drug-resistant cancer cells. Hence, we investigated the cytotoxic activities of 66 cardiotonic steroids and cardiotonic steroid derivatives in sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. Data were then subjected to quantitative structure-activity relationship analysis (QSA…
Chapter 6: Swelling of C6 glioma cells and astrocytes from glutamate, high K+ concentrations or acidosis
1992
Publisher Summary With impaired energy supply, cell swelling results from the failure of Na+/K+-ATPase according to the pump-leak model of cell volume regulation. In a series of in vitro studies, glial cell volume changes during defined and strictly controlled alterations of the extracellular environment in vitro. Experiments were performed with C6 glioma cells and astrocytes from primary culture. The major advantages of using C6 cells are the rapid availability of large cell numbers necessary for reliable flow cytometric volume measurements, and the homogeneous cell size distribution permitting the detection of even subtle volume changes. The sodium-potassium pump was blocked by the cardia…
Digitalis purpurea P5 beta R2, encoding steroid 5 beta-reductase, is a novel defense-related gene involved in cardenolide biosynthesis.
2009
The stereospecific 5 beta-reduction of progesterone is a required step for cardiac glycoside biosynthesis in foxglove plants. Recently, we have isolated the gene P5 beta R, and here we investigate the function and regulation of P5 beta R2, a new progesterone 5 beta-reductase gene from Digitalis purpurea. P5 beta R2 cDNA was isolated from a D. purpurea cDNA library and further characterized at the biochemical, structural and physiological levels. Like P5 beta R, P5 beta R2 catalyzes the 5 beta-reduction of the Delta(4) double bond of several steroids and is present in all plant organs. Under stress conditions or on treatment with chemical elicitors, P5 beta R expression does not vary, wherea…
�ber die Herzglykosid-artige Wirkung von Progesteronbisguanylhydrazon (Progesteronbiguazon)
1964
Die Wirkungen von Progesteronbisguanylhydrazon, g-Strophanthin und Digitoxigenin werden mit folgenden Methoden verglichen: Isolierte Vorhofe von Meerschweinchen, Ratten, Kaninchen und jungen Katzen; Herz-Lungen-Praparat des Meerschweinchens; cellulare Membran- und Aktionspotentiale von Vorhofmuskulatur; Natrium- und Kalium-Bestimmungen und Messung des Calcium-Umsatzes in isolierten Vorhofen von Meerschweinchen; isolierte Darmpraparate von Kaninchen und Meerschweinchen; Messung des Kalium-Gehaltes von „Kalteerythrocyten“ von Meerschweinchen, Kaninchen und Menschen. Ferner wird das Vergiftungsbild von Progesteronbisguanylhydrazon an der Maus beschrieben und gepruft, ob Cortisonbisguanylhydraz…
Isoform specificity of cardiac glycosides binding to human Na+,K+-ATPase α1β1, α2β1 and α3β1
2009
Abstract Cardiac glycosides inhibit the Na + ,K + -ATPase and are used for the treatment of symptomatic heart failure and atrial fibrillation. In human heart three isoforms of Na + ,K + -ATPase are expressed: α 1 β 1 , α 2 β 1 and α 3 β 1 . It is unknown, if clinically used cardiac glycosides differ in isoform specific affinities, and if the isoforms have specific subcellular localization in human cardiac myocytes. Human Na + ,K + -ATPase isoforms α 1 β 1 , α 2 β 1 and α 3 β 1 were expressed in yeast which has no endogenous Na + ,K + -ATPase. Isoform specific affinities of digoxin, digitoxin, β-acetyldigoxin, methyldigoxin and ouabain were assessed in [³H]-ouabain binding assays in the abse…
Cardiac Glycosides Exert Anticancer Effects by Inducing Immunogenic Cell Death
2012
Some successful chemotherapeutics, notably anthracyclines and oxaliplatin, induce a type of cell stress and death that is immunogenic, hence converting the patient's dying cancer cells into a vaccine that stimulates antitumor immune responses. By means of a fluorescence microscopy platform that allows for the automated detection of the biochemical hallmarks of such a peculiar cell death modality, we identified cardiac glycosides (CGs) as exceptionally efficient inducers of immunogenic cell death, an effect that was associated with the in- hibition of the plasma membrane Na + - and K + -dependent adenosine triphosphatase (Na + /K + -ATPase). CGs ex- acerbated the antineoplastic effects of DN…
Mediterranean Diet and Physical Activity Decrease the Initiation of Cardiovascular Drug Use in High Cardiovascular Risk Individuals: A Cohort Study
2021
Our aim was to assess whether long-term adherence to a Mediterranean diet (MedDiet) and leisure-time physical activity (LTPA) were associated with a lower initiation of cardiovascular drug use. We studied the association between cumulative average of MedDiet adherence and LTPA and the risk of cardiovascular drug initiation in older adults at high cardiovascular risk (PREvención con DIeta MEDiterránea trial participants) non-medicated at baseline: glucose-lowering drugs (n = 4437), antihypertensives (n = 2145), statins (n = 3977), fibrates (n = 6391), antiplatelets (n = 5760), vitamin K antagonists (n = 6877), antianginal drugs (n = 6837), and cardiac glycosides (n = 6954). One-point increas…