Anticancer Properties of Cardiac Glycosides

نویسنده

  • Varisa Pongrakhananon
چکیده

Cardiac glycosides comprise a large family of naturally derived compounds, the core struc‐ tures of which contain a steroid nucleus with a five-membered lactone ring (cardenolides) or a six-membered lactone ring (bufadienolides) and sugar moieties [1]. A few widely recognized examples of cardiac glycosides are digoxin, digitoxin, ouabain, and oleandrin. The cardeno‐ lides digitoxin and digoxin, two well-known cardiac glycosides, are inhibitors of the plasma membrane Na+/K+-ATPase that are clinically used for the treatment of heart failure. Their positive inotropic effects help suppress the active counter-transportation of Na+ and K+ across the cell membrane, leading to an increase in the intracellular Na+ concentration, a decrease in the intracellular K+ concentration, and a consequent increase in cardiac contraction [2]. Epidemiologic evidence suggests that breast cancer patients who were treated with digitalis have a significantly lower mortality rate, and their cancer cells had more benign characteristics than those from patients not treated with digitalis [3,4]. Interestingly, the concentrations of cardiac glycosides used for cancer treatment are extremely close to those found in the plasma of cardiac patients treated with the same drugs, suggesting that the anticancer effects of these drugs are exerted at non-toxic concentrations [5]. Furthermore, studies have suggested that cardiac glycosides target cancer cells selectively [6]. These encouraging findings have gained considerable attention in the field of anticancer research, and subsequent studies on the anticancer properties of these compounds have been conducted. These studies investigated not only digoxin and digitoxin but also other related cardiac glycosides, such as ouabain, oleandrin, proscillaridin A, and bufalin [7-10]. Several mechanisms of action, including the inhibition of cancer cell proliferation, the induction of apoptosis, and chemotherapy sensiti‐ zation, have been reported in a large number of published articles that support the potential use of these compounds for cancer treatment [11-14]. However, further clinical studies are still ongoing to better characterize the pharmacological and safety issues associated with these compounds. This chapter provides an overview of the anticancer activities of cardiac glyco‐

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تاریخ انتشار 2013