Cardiac Glycoside Drugs

1996 ◽  
pp. 99-123 ◽  
Keyword(s):  
Cardiac Glycoside

scholarly journals Structural Insights into the Interactions of Digoxin and Na+/K+-ATPase and Other Targets for the Inhibition of Cancer Cell Proliferation

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3672
Author(s):  
Yulin Ren ◽  
Sijin Wu ◽  
Joanna E. Burdette ◽  
Xiaolin Cheng ◽  
A. Douglas Kinghorn
Keyword(s):  
Cancer Cell ◽  
Cardiac Glycoside ◽  
Antitumor Agents ◽  
Docking Studies ◽  
Cancer Cell Proliferation ◽  
Antitumor Potential ◽  
Hydroxy Groups ◽  
Structural Insights ◽  
Side Pocket ◽  
Potential Use

Digoxin is a cardiac glycoside long used to treat congestive heart failure and found recently to show antitumor potential. The hydroxy groups connected at the C-12, C-14, and C-3′a positions; the C-17 unsaturated lactone unit; the conformation of the steroid core; and the C-3 saccharide moiety have been demonstrated as being important for digoxin’s cytotoxicity and interactions with Na+/K+-ATPase. The docking profiles for digoxin and several derivatives and Na+/K+-ATPase were investigated; an additional small Asn130 side pocket was revealed, which could be useful in the design of novel digoxin-like antitumor agents. In addition, the docking scores for digoxin and its derivatives were found to correlate with their cytotoxicity, indicating a potential use of these values in the prediction of the cancer cell cytotoxicity of other cardiac glycosides. Moreover, in these docking studies, digoxin was found to bind to FIH-1 and NF-κB but not HDAC, IAP, and PI3K, suggesting that this cardiac glycoside directly targets FIH-1, Na+/K+-ATPase, and NF-κB to mediate its antitumor potential. Differentially, digoxigenin, the aglycon of digoxin, binds to HDAC and PI3K, but not FIH-1, IAP, Na+/K+-ATPase, and NF-κB, indicating that this compound may target tumor autophagy and metabolism to mediate its antitumor propensity.

Demonstration and Characterization of two Classes of Cardiac Glycoside Binding Sites to Rat Heart Membrane Preparations Using Quantitative Computer Modeling

1987 ◽  
Vol 7 (5) ◽  
pp. 679-694
Author(s):  
Rudolf A. Lutz ◽  
David Lichtstein ◽  
Heng Xu ◽  
David Rodbard
Keyword(s):  
Computer Modeling ◽  
Cardiac Glycoside ◽  
Binding Sites ◽  
Rat Heart

Preparation of an analogue of orbicuside A, an unusual cardiac glycoside

2005 ◽  
Vol 16 (2) ◽  
pp. 393-401 ◽  
Author(s):  
John T. Dixon ◽  
Fanie R. van Heerden ◽  
Cedric W. Holzapfel
Keyword(s):  
Cardiac Glycoside

Membrane receptor calorimetry: cardiac glycoside interaction with Na,K-ATPase

2001 ◽  
Vol 380 (2) ◽  
pp. 245-254 ◽  
Author(s):  
E. Grell ◽  
E. Schick ◽  
E. Lewitzki
Keyword(s):  
Cardiac Glycoside ◽  
Membrane Receptor

Multiplicity of cardiac glycoside receptors in the heart

1985 ◽  
Vol 6 ◽  
pp. 293-295 ◽  
Author(s):  
Erland Erdmann ◽  
Karl Werdan ◽  
Lindsay Brown
Keyword(s):  
Cardiac Glycoside

The connection between the cardiac glycoside‐induced senescent cell morphology and Rho/Rho kinase pathway

Cytoskeleton ◽  
2018 ◽  
Vol 75 (11) ◽  
pp. 461-471 ◽  
Author(s):  
Yaprak Dilber Şimay ◽  
Aysun Özdemir ◽  
Burçin İbişoğlu ◽  
Mustafa Ark
Keyword(s):  
Cell Morphology ◽  
Cardiac Glycoside ◽  
Rho Kinase ◽  
Senescent Cell ◽  
Kinase Pathway

scholarly journals Ouabain, a Cardiac Glycoside, Inhibits the Fanconi Anemia/BRCA Pathway Activated by DNA Interstrand Cross-Linking Agents

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e75905 ◽  
Author(s):  
Dong Wha Jun ◽  
Mihwa Hwang ◽  
Hyun Jung Kim ◽  
Soo Kyung Hwang ◽  
Sunshin Kim ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Cardiac Glycoside ◽  
Cross Linking

scholarly journals The Cardiac Glycoside Deslanoside Exerts Anticancer Activity in Prostate Cancer Cells by Modulating Multiple Signaling Pathways

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5809
Author(s):  
Mingcheng Liu ◽  
Qingqing Huang ◽  
Jun A ◽  
Linyue Li ◽  
Xiawei Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Anticancer Activity ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Cardiac Glycoside ◽  
Cardiac Glycosides ◽  
Disease Free Survival ◽  
Diverse Range ◽  
Multiple Signaling

Prostate cancer (PCa) is a leading cause of cancer-related deaths among men worldwide, and novel therapies for advanced PCa are urgently needed. Cardiac glycosides represent an attractive group of candidates for anticancer repurposing, but the cardiac glycoside deslanoside has not been tested for potential anticancer activity so far. We found that deslanoside effectively inhibited colony formation in vitro and tumor growth in nude mice of PCa cell lines 22Rv1, PC-3, and DU 145. Such an anticancer activity was mediated by both the cell cycle arrest at G2/M and the induction of apoptosis, as demonstrated by different functional assays and the expression status of regulatory proteins of cell cycle and apoptosis in cultured cells. Moreover, deslanoside suppressed the invasion and migration of PCa cell lines. Genome-wide expression profiling and bioinformatic analyses revealed that 130 genes were either upregulated or downregulated by deslanoside in both 22Rv1 and PC-3 cell lines. These genes enriched multiple cellular processes, such as response to steroid hormones, regulation of lipid metabolism, epithelial cell proliferation and its regulation, and negative regulation of cell migration. They also enriched multiple signaling pathways, such as necroptosis, MAPK, NOD-like receptor, and focal adhesion. Survival analyses of the 130 genes in the TCGA PCa database revealed that 10 of the deslanoside-downregulated genes (ITG2B, CNIH2, FBF1, PABPC1L, MMP11, DUSP9, TMEM121, SOX18, CMPK2, and MAMDC4) inversely correlated, while one deslanoside-upregulated gene (RASD1) positively correlated, with disease-free survival in PCa patients. In addition, one deslanoside-downregulated gene (ENG) inversely correlated, while three upregulated genes (JUN, MXD1, and AQP3) positively correlated with overall survival in PCa patients. Some of the 15 genes have not been implicated in cancer before. These findings provide another candidate for repurposing cardiac glycosides for anticancer drugs. They also suggest that a diverse range of molecular events underlie deslanoside’s anticancer activity in PCa cells.

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