Contrasting effects of cardiac glycosides on cisplatin- and etoposide-induced cell death

  title={Contrasting effects of cardiac glycosides on cisplatin- and etoposide-induced cell death},
  author={Andrey V. Kulikov and Ekaterina A Slobodkina and A. V. Alekseev and Vladimir Gogvadze and Boris Zhivotovsky},
  journal={Biological Chemistry},
  pages={661 - 670}
Abstract Cardiac glycosides (CGs) or cardiotonic steroids, which constitute a group of naturally occurring compounds with a steroid-like structure, can act on Na+/K+-ATPase as a receptor and activate intracellular signaling messengers leading to a variety of cellular responses. Epidemiological studies have revealed that CGs, used for the treatment of cardiac disorders, may also be beneficial as anti-cancer agents. CGs, acting in combination with other chemotherapeutic agents, may significantly… 

Figures from this paper

Cardiac glycosides: From molecular targets to immunogenic cell death

Involvement of Src signaling in the synergistic effect between cisplatin and digoxin on cancer cell viability

It is demonstrated that the interaction between cisplatin and digoxin had a synergistic effect on cervical cancer cells and a significantly positive cytotoxic and antiproliferative effect on this cell line compared to the control and single cisPlatin treatments.

Na+/K+-ATPase as a target for cardiotonic steroids and cisplatin

The structure, function, and enzymatic reaction of Na/K-ATPase, as well as the potential for the pump to serve as a target for ouabain and cisplatin are summarized.



Cardiac glycosides in cancer research and cancer therapy.

There is growing interest in evaluating the oleander products and possibly other cardiac glycosides as antineoplastic agents and the first of these therapies to be developed in the United States is a patented, water-soluble oleanders extract called Anvirzel.

Cardiac glycosides induce resistance to tubulin-dependent anticancer drugs in androgen-independent human prostate cancer.

It is suggested that cardiac glycosides inhibit the G2/M arrest induced by tubulin-binding anticancer drugs via an indirect blockade on microtubule function, and the decline in transport of these drugs into the nucleus may partly explain the action of cardiac Glycosides.

Cardiotonic steroids attenuate ERK phosphorylation and generate cell cycle arrest to block human hepatoma cell growth

Antineoplastic activity of ouabain and pyrithione zinc in acute myeloid leukemia

The results suggest that PZ and OUA may exhibit antileukemic effects by inducing the apoptotic demise of AML cells.

Digoxin and other cardiac glycosides inhibit HIF-1α synthesis and block tumor growth

Digoxin administration increased latency and decreased growth of tumor xenografts, whereas treatment of established tumors resulted in growth arrest within one week, demonstrating that HIF-1 is a critical target of digoxin for cancer therapy.

Digitoxin is a potential anticancer agent for several types of cancer.

  • J. Haux
  • Biology
    Medical hypotheses
  • 1999
The ability of digitalis to block cell proliferation has been well established for some time. Recently, digitalis in non-toxic concentrations has been showed to induce apoptosis in different

Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells.

It is reported that the cardiac glycosides oleandrin, ouabain, and digoxin induce apoptosis in androgen-independent human prostate cancer cell lines in vitro, defining a novel activity for cardiac Glycosides that could prove relevant to the treatment of metastatic prostate cancer.

Cardiotonic steroids-mediated Na+/K+-ATPase targeting could circumvent various chemoresistance pathways.

The aims of this review are to examine the various molecular pathways by which the NaK targeting can be more deleterious to biologically aggressive cancer cells than to normal cells.

Cardiac glycosides initiate Apo2L/TRAIL-induced apoptosis in non-small cell lung cancer cells by up-regulation of death receptors 4 and 5.

It is reported that cardiac glycosides, which have been used for the treatment of cardiac failure for many years, sensitize lung cancer cells but not normal human peripheral blood mononuclear cells to Apo2L/TRAIL-induced apoptosis.