Steroid Glycosides Hyrcanoside and Deglucohyrcanoside: On Isolation, Structural Identification, and Anticancer Activity

Abstract

Cardiac glycosides (CGs) represent a group of sundry compounds of natural origin. Most CGs are potent inhibitors of Na+/K+-ATPase, and some are routinely utilized in the treatment of various cardiac conditions. Biological activities of other lesser known CGs have not been fully explored yet. Interestingly, the anticancer potential of some CGs was revealed and thereby, some of these compounds are now being evaluated for drug repositioning. However, high systemic toxicity and low cancer cell selectivity of the clinically used CGs have severely limited their utilization in cancer treatment so far. Therefore, in this study, we have focused on two poorly described CGs: hyrcanoside and deglucohyrcanoside. We elaborated on their isolation, structural identification, and cytotoxicity evaluation in a panel of cancerous and noncancerous cell lines, and on their potential to induce cell cycle arrest in the G2/M phase. The activity of hyrcanoside and deglucohyrcanoside was compared to three other CGs: ouabain, digitoxin, and cymarin. Furthermore, by in silico modeling, interaction of these CGs with Na+/K+-ATPase was also studied. Hopefully, these compounds could serve not only as a research tool for Na+/K+-ATPase inhibition, but also as novel cancer therapeutics.

The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

“…Thus far, a large number of natural compounds have been identified to have anti-tumor effects. The action mechanisms of these compounds are varied, including inducement of endoplasmic reticulum stress and cell cycle arrest, inhibition of ATPase and protein synthesis, and promotion of apoptosis [ 30 , 31 , 32 , 33 , 34 ]. Ginsenosides, the main active ingredients in ginseng, have been suggested to have therapeutic effects on a variety of human diseases, such as senescence, hyperglycemia, hypertension, hypoimmunity, and cancer.…”

Cardiac Glycosides as Immune System Modulators

“…Among such potential repurposed drug candidates belong, for example, cardiac glycosides (CGs), currently used in clinical practice for the treatment of heart diseases, such as congestive heart failure or cardiac arrhythmias. Furthermore, CGs also 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 not only for cancer treatment but also in the treatment of a plethora of autoimmune and inflammatory diseases.…”

Quo vadis Cardiac Glycoside Research?

“…CGs as plant toxins have been known to mankind for centuries and during that time, they have built up a solid place in pharmacy as drugs for the treatment of heart failure and arrhythmias due to their positive inotropic effect on the heart muscle cells. Besides, they have been shown to be cytotoxic or to suppress cancer cell proliferation [ 143 ] by interacting with NKA by mechanisms that differ from their action on healthy cells. The first part of this review article focuses on the occurrence of CGs and the optimization of their production, which is still a major challenge, as CGs are currently still isolated from plants, unlike many other drugs that are produced by organic synthesis or microbial biotechnology.…”