Cardiac Glycosides as Immune System Modulators

Škubník, Jan; Pavlíčková, Vladimíra Svobodová; Rimpelová, Silvie

doi:10.3390/biom11050659

Cited by 28 publications

(21 citation statements)

References 80 publications

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“…The next part was devoted to the CG structure concerning their ability to interact with NKA. This research is connected with the study of CGs as anticancer drugs [ 144 , 145 ]. The therapeutic window of these compounds is very narrow, which complicates their use in clinical practice not only in the field of cardiology but also as potential anticancer drugs.…”

Section: Discussionmentioning

confidence: 99%

Quo vadis Cardiac Glycoside Research?

Bejček

Jurášek

Spiwok

et al. 2021

Toxins

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Cardiac glycosides (CGs), toxins well-known for numerous human and cattle poisoning, are natural compounds, the biosynthesis of which occurs in various plants and animals as a self-protective mechanism to prevent grazing and predation. Interestingly, some insect species can take advantage of the CG’s toxicity and by absorbing them, they are also protected from predation. The mechanism of action of CG´s toxicity is inhibition of Na+/K+-ATPase (the sodium-potassium pump, NKA), which disrupts the ionic homeostasis leading to elevated Ca2+ concentration resulting in cell death. Thus, NKA serves as a molecular target for CGs (although it is not the only one) and even though CGs are toxic for humans and some animals, they can also be used as remedies for various diseases, such as cardiovascular ones, and possibly cancer. Although the anticancer mechanism of CGs has not been fully elucidated, yet, it is thought to be connected with the second role of NKA being a receptor that can induce several cell signaling cascades and even serve as a growth factor and, thus, inhibit cancer cell proliferation at low nontoxic concentrations. These growth inhibitory effects are often observed only in cancer cells, thereby, offering a possibility for CGs to be repositioned for cancer treatment serving not only as chemotherapeutic agents but also as immunogenic cell death triggers. Therefore, here, we report on CG´s chemical structures, production optimization, and biological activity with possible use in cancer therapy, as well as, discuss their antiviral potential which was discovered quite recently. Special attention has been devoted to digitoxin, digoxin, and ouabain.

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Section: Discussionmentioning

confidence: 99%

Quo vadis Cardiac Glycoside Research?

Bejček

Jurášek

Spiwok

et al. 2021

Toxins

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“…Cardiac glycosides including digitoxin, digoxin, ouabain, and their convolution have a profound influence in inhibiting viral proliferation and may be effective in virus-associated tumors. CGs intermediates and their mode of action as immune modulators [ 188 ] and other cytotoxic activities [ 134 ] have also been reported and need further evaluation. A highly specialized targeted deep ML tool could probably address the question of identifying potential candidates within the available CG database.…”

Section: Novel Aspects Of Cardiac Glycoside Researchmentioning

confidence: 99%

Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics

et al. 2021

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Cardiac glycosides are natural sterols and constitute a group of secondary metabolites isolated from plants and animals. These cardiotonic agents are well recognized and accepted in the treatment of various cardiac diseases as they can increase the rate of cardiac contractions by acting on the cellular sodium potassium ATPase pump. However, a growing number of recent efforts were focused on exploring the antitumor and antiviral potential of these compounds. Several reports suggest their antitumor properties and hence, today cardiac glycosides (CG) represent the most diversified naturally derived compounds strongly recommended for the treatment of various cancers. Mutated or dysregulated transcription factors have also gained prominence as potential therapeutic targets that can be selectively targeted. Thus, we have explored the recent advances in CGs mediated cancer scope and have considered various signaling pathways, molecular aberration, transcription factors (TFs), and oncogenic genes to highlight potential therapeutic targets in cancer management.

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“…Inflammation, besides cardiac and cancer diseases, is another condition that can potentially be treated with CGs. The impact of CGs on the immune system and inflammation progression has been reviewed elsewhere, see reference [ 30 ]. The latter three conditions are, however, not the only ones in the therapeutic portfolio of CGs.…”

Section: Cardiac Glycosides and Their Targetmentioning

confidence: 99%

“…Both proteins then form a scaffold for further signaling cascade proteins, such as Src homology 2 domain-containing transforming protein 1, growth factor receptor-bound protein 2, son of sevenless protein, and ras. At the end of this complex signaling pathway, processes, such as the formation of reactive oxygen species (ROS) leading to apoptosis or autophagy, are triggered [ 30 ]. In particular, autophagy plays an important role in viral infections and, thus, its induction by CGs may be beneficial in the antiviral treatment [ 64 ].…”

Section: Effects Of Cgs On Viral Life Cyclementioning

confidence: 99%

Repurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses

et al. 2021

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Drug repositioning is a successful approach in medicinal research. It significantly simplifies the long-term process of clinical drug evaluation, since the drug being tested has already been approved for another condition. One example of drug repositioning involves cardiac glycosides (CGs), which have, for a long time, been used in heart medicine. Moreover, it has been known for decades that CGs also have great potential in cancer treatment and, thus, many clinical trials now evaluate their anticancer potential. Interestingly, heart failure and cancer are not the only conditions for which CGs could be effectively used. In recent years, the antiviral potential of CGs has been extensively studied, and with the ongoing SARS-CoV-2 pandemic, this interest in CGs has increased even more. Therefore, here, we present CGs as potent and promising antiviral compounds, which can interfere with almost any steps of the viral life cycle, except for the viral attachment to a host cell. In this review article, we summarize the reported data on this hot topic and discuss the mechanisms of antiviral action of CGs, with reference to the particular viral life cycle phase they interfere with.

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Cardiac Glycosides as Immune System Modulators

Cited by 28 publications

References 80 publications

Quo vadis Cardiac Glycoside Research?

Quo vadis Cardiac Glycoside Research?

Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics

Repurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses

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