Abstract
Cardiac glycosides (CGs) are natural steroid compounds occurring both in plants and animals. They are known for long as cardiotonic agents commonly used for various cardiac diseases due to inhibition of Na+/K+-ATPase (NKA) pumping activity and modulating heart muscle contractility. However, recent studies show that the portfolio of diseases potentially treatable with CGs is much broader. Currently, CGs are mostly studied as anticancer agents. Their antiproliferative properties are based on the induction of multiple signaling pathways in an NKA signalosome complex. In addition, they are strongly connected to immunogenic cell death, a complex mechanism of induction of anticancer immune response. Moreover, CGs exert various immunomodulatory effects, the foremost of which are connected with suppressing the activity of T-helper cells or modulating transcription of many immune response genes by inhibiting nuclear factor kappa B. The resulting modulations of cytokine and chemokine levels and changes in immune cell ratios could be potentially useful in treating sundry autoimmune and inflammatory diseases. This review aims to summarize current knowledge in the field of immunomodulatory properties of CGs and emphasize the large area of potential clinical use of these compounds.
Highlights
cardiac glycosides (CGs) are potent Na+ /K+ -ATPase (NKA) inhibitors, which have long been used in cardiac medicine
What makes CGs exceptional among other anticancer drug candidates such as antimitotics [82,83]? In this review article, we showed that the great advantage of CGs in anticancer treatment is the induction of Immunogenic cell death death (ICD)
CGs might be an excellent option in combinatorial treatment, as they can efficiently eliminate cancer cells surviving after conventional treatment
Summary
According to the Global Cancer Observatory study (GLOBOCAN) 2020, it is estimated that in 2020, there was an increase of 19.3 million new cases of cancer, half of which lead to patient death. CGs exert very promising anticancer activity both in vitro and in vivo [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18], which is based mainly on the induction of complex signaling cascades in Na+ /K+ -ATPase (NKA) signalosome and induction of immune response This fact could be utilized for cancer treatment and in the treatment of a plethora of autoimmune and inflammatory diseases.
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