Medicine: Digitalis

Digitalis, otherwise known as foxglove, is one of the most famous medicinal plants in human history. In the late 1700s it was identified as a medicine for what was then called dropsy, and which is now referred to as congestive heart failure. It was a medicine that allegedly made the heart glad. In the next two centuries, it became one of the most widely used plants for all manner of heart illnesses. The beautiful foxglove healed the failing heart; it resolved hearts that were beating too fast or too irregularly. Its effects were rapid, and in those with failing or irregular hearts, the effects were almost miraculous.

Digitalis has also been known as a potentially dangerous plant in that taking too much leaves the patient with nausea, anorexia (no appetite), visual disturbances (especially seeing blue halos around lights) and eventually even heart arrythmias and death. Digitalis leaves contain a wide array of constituents, including the main alkaloids digoxin and digitoxin. Currently it is thought that the main effect of digitalis on the heart is from digoxin, which is now prescribed in the semi-synthetic form of Lanoxin.

Some years ago many physicians noticed that their patients on digitalis preparations, especially those made from whole-leaf preparations which contain both digoxin and digitoxin, suffered from much less cancer, or recurrences of pre-existing cancers, than other patients. I share with you below some of the studies that confirm these observations, and some of the biochemical reasons why this effect may occur. For example, one study found that the recurrence rate of women with breast cancer on digitalis was less than 5% compared to about 30% of those not on digitalis. Other studies have confirmed this same result. Since the cancer therapy effect of digitalis is not thought to be found in the digoxin, but rather in the whole-leaf extract, that is the form that I use.

Please follow the directions for the use of digitalis carefully, as this is a plant that needs our utmost respect and care.

Following is information for those who wish to read further on the uses of digitalis, including selected papers from the National Library of Medicine and other sources, and several websites that might be of interest.

FYI, I have had numerous requests from patients who are undergoing treatment for cancer, particularly Iscador therapy, who would like to talk with other patients about their experiences. We want to act as a conduit to put people in touch with one another so they can get more information and share stories. The focus of this  cancer discussion forum is on patients and their experiences. It will be wholly the effort of those who have an interest. I will not be involved in any way except as the initial facilitator for putting people together through a confidential email exchange. Click here for more information

Please note that this material is for informational and educational purposes only and is not intended to replace consultation with a doctor.


Selected Papers - Click on Abstracts to read more via links.

Involvement of Cdk5/p25 in digoxin-triggered prostate cancer cell apoptosis. Lin H, Juang JL, Wang PS. Division of Molecular and Genomic Medicine, National Health Research Institutes, Taipei 115, Taiwan, Republic of China.J Biol Chem. 2004 Jul 9;279(28):29302-7. Epub 2004 Apr 30. 

Abstract
This study’s results suggest that Cdk5/p35 and p25 are novel players in digoxin-triggered prostate cancer cell apoptosis and, therefore, become potential therapeutic targets.

PMID: 15123618


Anti-tumour activity of Digitalis purpurea L. subsp. heywoodii. Lopez-Lazaro M, Palma De La Pena N, Pastor N, Martin-Cordero C, Navarro E, Cortes F, Ayuso MJ, Toro MV. Departamento de Farmacologia, Facultad de Farmacia, Universidad de Sevilla, Spain. Planta Med. 2003 Aug;69(8):701-4. 

Abstract
Four extracts obtained from the leaves of Digitalis purpurea subsp. heywoodii have been assessed for cytotoxic activity against three human cancer cell lines.

PMID: 14531018


The dynamics of cell proliferation. John F. Moxnes, Johan Haux and Kjell Hausken Received 7 Mar 2003; accepted 23 Dec 2003. Available online 27 Feb 2004. 

Abstract (from ScienceDirect.com)
The article provides a mathematical description based on the theory of differential equations, for the proliferation of malignant cells (cancer).


Digitalis; impinges on more than just the (ion-) pump.Haux J Department of Oncology, St Olav’s University Hospital, Trondheim, Norway.Medical Hypotheses, Volume 59, Issue 6 , 12 November 2002, Pages 781-782

Abstract
Digitalis has complex dose-dependent mechanisms of action involving many signaling systems and the relevance of this for the anticancer effects are discussed.

PMID: 12445525


Digitoxin medication and cancer; case control and internal dose-response studiesHaux J, Klepp O, Spigset O, Tretli S. Department of Oncology, University Hospital, N-7006, Trondheim, Norway.BMC Cancer. 2001;1(1):11. Epub 2001 Aug 10. 

Abstract
This paper investigates if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population.

PMID: 11532201


Digitoxin decreases cell growth and may work as radiosensitizer in glioblastoma cell linesABL Marthinsen PhD, T Strickert MSc, KM Jensen MSc, J Haux MDCancer Detection and Prevention 2000;24(Supplement 1). 

Abstract
Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 – 31, 2000; in the section on synergistic therapies.


Digitoxin is a potential anticancer agent for several types of cancerJ. Haux Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim, Norway Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim.Med Hypotheses. 1999 Dec;53(6):543-8.

Abstract

This article studies features of the cardiac glycosides which make them interesting to evaluate further as potential anticancer drugs are discussed. Some new data concerning inhibition and apoptosis in three human glioblastoma cell lines by digitoxin are also presented.

Publication Types: Review, Tutorial

PMID: 10687899


Digitoxin, in non-toxic concentrations, inhibits proliferation and induces cell death in prostate cancer cell lines 

Haux J, Solheim O, Isaksen T, Angelsen A.Z-ONKOL. Zeitschrift für Onkologie. 2000; 32/1 (11-16)

Abstract
In an earlier study we found apoptosis induction in human leukemia cell lines by digitoxin. The main known pharmacological effect of digitoxin is Na+/K+ATPase inhibition. In fact, the Na+/K+ATPase has been proposed to be the actual androgen receptor of the prostate. Hence, it is of interest to examine the effects of the clinically used cardiac glycosides digoxin and digitoxin on human prostate cancer cell lines. In the present study we assessed the cancer prostate cancer cell lines LNCaP, PC-3, TSU-pr1 and DU-145 for susceptibility to digoxin and digitoxin. Digoxin, in clinically relevant concentrations, induced minor inhibition of viability, whereas digitoxin potently inhibited all 4 cell lines. DNA histogram analysis revealed an accumulation of the digitoxin treated cells in the G2M phase of the cell cycle as well as DNA fragmentation. Proliferation data, MTT data and DNA histograms together with phase contrast light microscopy indicated cell death induced through apoptosis. These results imply a possible role for cardiac glycosides in the management of prostate cancer.


Digitoxin, in non toxic concentrations, induces apoptotic cell death in Jurkat T cells in vitro. 

Haux J, Lam M, Marthinsen ABL, Strickert T, Lundgren S. Z-ONKOL. Zeitschrift für Onkologie. 1999; 31/1 (14-20).

Abstract
Reports concerning the anti-cancer effects of digitalis interested us in performing an in vitro study of digitoxin and digoxin on 5 different malignant cell lines. Two breast cancer cell lines, MDA-MB-231 (receptor negative), T47D (receptor positive) and three malignant hematological cell lines, Jurkat, Daudi and K562, were tested for sensitivity for digitoxin and digoxin.

Peripheral blood mononuclear cells (PBMC) and natural killer cells (NK), both non stimulated and interleukin 2 (IL-2) stimulated, were used as control cells. Digitoxin has growth inhibitory effects on both breast cancer cell lines and inhibited proliferation and decreased viability of two of the three malignant hematological cell lines tested. Digitoxin exerted these effects in therapeutic concentrations for treating cardiac congestion. In the hematological cell lines Jurkat and Daudi digitoxin induced apoptotic cell death. PBMC and NK cells, both non-stimulated and IL-2 stimulated, were not affected by the same concentrations of digitoxin. Digoxin also showed inhibiting properties on the malignant cell lines, but the effects were less pronounced and not dose dependent. Digitoxin may be a prototype anticancer drug exerting its effect through a mechanism other than cytotoxicity.


Digitoxin sensitizes malignant breast cancer cells for radiation in vitro.

Haux J, Marthinsen ABL, Gulbrandsen M, Alfredsen AS, Johansen H, Strickert T, Lundgren S.Z-ONKOL. Zeitschrift für Onkologie. 1999; 31/3 (61-65).

Abstract
The malignant breast cancer cell lines T47D and MDA-MB-231 were examined for altered radiosensitivity during treatment with the cardiac glycosides digoxin and digitoxin. The effects were assessed with a clonogenic assay and DNA histograms. Digitoxin sensitized both cell lines for radiation when applied at least 3 days before radiation. Digoxin also induced changes in radiosensitivity, but not to the same extent. Digitoxin seem to halt T47D and MDA-MB-231 in the G2M phase of the cell cycle and this may be one explanation for the increased radiosensitivity.


The role of interleukin-2 in regulating the sensitivity of natural killer cells for Fas-mediated apoptosis.

Haux J, Johnsen AC, Steinkjer B, Egeberg K, Sundan A, Espevik T Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim.Cancer Immunol Immunother 1999 May-Jun;48(2-3):139-46

Abstract
Study of the role that Fas/Fas-ligand (FasL) system seems to play a key role in regulating immunoresponses.

PMID: 10414468


Regulation of APO-2 ligand/trail expression in NK cells-involvement in NK cell-mediated cytotoxicity. 

Johnsen AC, Haux J, Steinkjer B, Nonstad U, Egeberg K, Sundan A, Ashkenazi A, Espevik T. Department of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim, Norway.Cytokine. 1999 Sep;11(9):664-72. Related Articles, Links 

Abstract
A study that shows that Apo-2L is expressed and utilized by human Natural Killer (NK) cells.

PMID: 10479402


Regulation of Fas and Fas-ligand expression in NK cells by cytokines and the involvement of Fas-ligand in NK/LAK cell-mediated cytotoxicity.

Medvedev AE, Johnsen AC, Haux J, Steinkjer B, Egeberg K, Lynch DH, Sundan A, Espevik T. Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim, Norway. Cytokine. 1997 Jun;9(6):394-404.

Abstract
This study demonstrates cytokine-mediated regulation of Fas and Fas-ligand (Fas-L) expression in human NK cells and the involvement of the Fas-L pathway in NK/LAK cytotoxicity.

PMID: 9199873


Inhibitory effects of digitalis on the proliferation of androgen dependent and independent prostate cancer cells. 

Yeh JY, Huang WJ, Kan SF, Wang PS. Department and Graduate Institute of Physiology, School of Life Science, National Yang-Ming University, Taipei, Taiwan, Republic of China.  J Urol. 2001 Nov;166(5):1937-42. 

Abstract
Study evaluating the effects and underlying mechanisms of cardiac glycosides, including digoxin, digitoxin and ouabain, on the proliferation of hormone dependent and independent prostate cancer cell lines.

PMID: 11586264


Is digitalis a therapy for breast carcinoma? Stenkvist B. Institute of Pathology, University of Uppsala, Uppsala, Sweden. Oncol Rep. 1999 May-Jun;6(3):493-6. 

Abstract
Long-term follow-up (22.3 years) of 175 patients with breast carcinoma, of which 32 were on digitalis treatment, when they acquired their breast carcinoma.

PMID: 10203580


Evidence of a modifying influence of heart glucosides on the development of breast cancer. 

Stenkvist B, Bengtsson E, Eklund G, Eriksson O, Holmquist J, Nordin B, Westman-Naeser S.Anal Quant Cytol. 1980 Mar-Apr;2(1):49-54. 

Abstract
Patients on digitalis medication at the time of diagnosis of breast cancer seem to develop tumors that have a lower growth potential than do patients not on such medication. These tumors are photometrically characterized by small nuclei with lower DNA-RNA content and less variation in morphometric characteristics.

PMID: 7377665


Several websites provide additional information on the therapeutic use of digitalis.