Digitalis: The Insulin for Cancer?

 

Digitalis, a heart drug, also is an anticancer agent with properties of inducing apoptosis and inhibiting proliferation of cancer cells. This is confirmed by a new study that found very low cancer mortality in many cardiac patients taking digitalis

 

ICP, April 20, 2006 --- Coronary heart disease is the prime motivation of the Infarct Combat Project (ICP). However, there are paramount cases in other medical conditions which ICP can’t neglect its participation and contribution. The present news is related with the use of an effective and inexpensive heart drug, for the treatment of cancer.

 

In a paper published in 2002 at Ars Cvrandi, a Brazilian medical journal, it was perceived an exceptional low mortality by cancer in cardiac patients treated with digitalis or other cardiac glycosides, when used in prevention of cardiac failure, unstable angina, acute myocardial infarction and sudden death.

 

This case study involved 1150 patients with stable coronary heart disease. The follow-up period was 28 years. The cardiac glycosides employed were: Digitoxin, Digoxin, Acetyldigoxin, Betametyldigoxin, Proscillaridin-A or Lanatoside-C at daily therapeutic oral doses - non toxic, preferably lower.

 

It was shown in this study that the global mortality for the patients without previous myocardial infarction was 14.2% (0.5% per year) while the global mortality for the patients with previous myocardial infarction was 41.0% (1.4% per year). Surprisingly, the cancer mortality in these patients treated with digitalis or other cardiac glycosides was just 1.7% in total.

 

This curious information prompted ICP to verify the cancer mortality rate for patients in similar medical condition and age, presented in other studies. Also, it was made a search at Medline, founding many studies showing digitalis as anticancer drug, with properties of inducing apoptosis (cell death) and inhibiting proliferation of cancer cells.

 

For the cancer mortality comparison the data was taken from a large study which had a follow-up of 5 years, involving 20.536 patients aged 40-80 years with coronary heart disease, other vascular diseases or diabetes. The bench-mark study found a cancer mortality of 3.3% (0.7% per year), in patients taking statin or placebo (inactive substance), while the study using digitalis or other cardiac glycosides, found a much lower mortality rate for cancer (0.06% per year)..

 

Unfortunately, the astonishing finding of extremely low cancer mortality in the cardiac patients taking digitalis couldn’t be explored in the study signed by Quintiliano de Mesquita and Claudio Baptista. Cancer was not its main focus and a control group for this purpose is lacking.

 

Studies pointing a reduction in mortality by cancer in patients taking digitalis are not new. In fact there are some writings stating that in the beginning of the past century the first study about this relationship was happened. Anyway, just in recent years the scientific confirmation came, suggesting digitalis as a potential anticancer agent. 

 

Perhaps the actual lack of interest on using of digitalis and other cardiac glycosides, as anticancer agents, start to change from now on with the development in US of a new technique, called neoglycorandomization.  This scientific approach allows the manipulation of these drugs composition in their molecular structure, enhancing its capacity to fight malignant cells. Certainly this new technique, permitting the creation of patentable formulas for the tweak digitalis, will generate huge interests by the pharmaceutical companies, deeply affecting the research of new drugs, with the “rediscovery” of digitalis to fight coronary heart disease and cancer.

 

It is remarkable that during the past few years many patents applications were filled in US, related to the use of some cardiac glycosides (digoxin, digitoxin, oleandrin, ouabain, etc) when indicated in the treatment of cancer including in conjunction with other methods like radiotherapy.

 

In addition, it was developed, very recently, an extraordinary hypothesis that seems to fit perfectly well in the idea of digitalis as the “insulin” for cancer. It postulates that alterations in the metabolism of endogenous digitalis-like compounds* and in their interactions with the Na/K-ATPase (Sodium/Potassium pump) may be associated with the development of cancer.

 

* Endogenous digitalis-like compounds of the cardenolide (digoxin and ouabain) and bufadienolide (Proscilaridine-A and Marinobufagenin) types have been recently isolated from human tissues and body fluids, showing the same molecular structure of cardiac glycosides extracted from plants.

 

Some additional notes (Nov 29, 2006):

1) Stress hormones and cancer

Recent studies found a strong link between stress hormones and increased growth rate of cancer. This may explain in part the efficacy of digitalis and other cardiac glycosides, by blocking the excessive release of norepinephrine during stress situations, in the treatment of cancer (26, 27, 28, 29).

2) Clinical studies in progress, registered at Clinicaltrials.gov:
a) Involvement of Endogenous Digitalis-Like Compounds in Breast Cancer, Heidrun Weidemann et al. April 4, 2006,
http://www.clinicaltrials.gov/ct/show/NCT00310882
b) Second Line Erlotinib (Tarceva) Plus Digoxin in Non-Small Cell Lung Cancer, Goetz H Kloecke et al. January 23, 2006 http://www.clinicaltrials.gov/ct/show/NCT00281021?order=1

 

__________________________________________________

 

Infarct Combat Project is an international non-profit organization that provides information, research and education to fight heart disease. The ICP homepage is http://www.infarctcombat.org

__________________________________________________

 

 

References:

  1. Cardiotônico: Insuperável na Preservação da Estabilidade Miocárdica como Preventivo das Síndromes Coronárias Agudas e Responsável pela Prolongada Sobrevida -- Casuística de 28 anos (1972-2000), Mesquita, QHde e Baptista, CAS.  Ars Cvrandi, Volume 35 - nº 3 - maio de 2002.  Republished at Internet, 2005 -- http://www.infarctcombat.org/28anos/digitalicos.html with a summary in English at http://www.infarctcombat.org/heartnews-16.html

  2. A New Explanation Strengthen an Old Remedy and Shed Light to the Coronary Heart Disease Enigma, ICPwire, April 5, 2006 at http://www.infarctcombat.org/media/040506.html

  3. “Two Heart Disease Theories, Same Therapeutic Treatment”, by Carlos Monteiro, ICP, with comments by Dr. Thomas Cowan, Fourfold Healing Newsletter of November/December/05 http://www.fourfoldhealing.com/NL%20NovDec%202005.htm and bibliography at http://www.infarctcombat.org/FH2005-ref.html

  4. Digitalis's anticancer effects, by Carlos Monteiro, ICP, Townsend Letter for Doctors And Patients, May 2006 http://www.tinyurl.com/r932g

  5. The effects of cholesterol lowering with simvastatin on cause-specific mortality and on cancer incidence in 20,536 high-risk people: a randomized placebo-controlled trial, Heart Protection Study Collaborative Group. BMC Medicine 2005, 3:6 --http://www.biomedcentral.com/1741-7015/3/6 (Table 2)

  6. Cardiac glycosides and breast cancer revisited, Stenkvist B, N Engl J Med 1982 Feb 25;306(8):484

  7. Digitalis and cancer, Goldin AG, Safa AR, Letter, Lancet 1984 Oct 13;2(8407):875

  8. Is digitalis a therapy for breast carcinoma? Stenkvist B, Oncol Rep. 1999 May-Jun;6(3):493-6 -- http://tinyurl.com/7b9m9

  9. Cardiac Glycosides vs Alkylating Agents in Medical Oncology, Letter from Johan Haux. Townsend Letter for Doctors And Patients, Oct 2000 --http://www.cancerwire.com/HauxTLDPdec2000.pdf

  10. Digitalis is the right drug being used to treat the wrong disease. Wayne Martin, Barry Groves, Second Opinions, 2000 -- http://www.second-opinions.co.uk/heart_drugs.html

  11. Digitoxin in non-toxic concentrations, inhibits proliferation and induces cell death in Jurkat T cells in vitro, Haux et al. Z-Onkol, 1999, 31 (1):14-20

  12. Digitoxin is a potential anticancer agent for several types of cancer, Haux J, Med Hypotheses 1999 Dec; 53(6):543-8 -- http://tinyurl.com/e2pkt

  13. Digitoxin in non-toxic concentrations, inhibits proliferation and induces cell death in prostate cell lines, Haux et al. Z-Onkol, 2000, 32 (1):11-16

  14. Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells, McConkey DJ et al Cancer Res. 2000 Jul 15,60(14):3807-12 -- http://cancerres.aacrjournals.org/cgi/content/full/60/14/3807

  15.  Anticancer effect of digitoxin, Wayne Martin,  Townsend Letter for Doctors And Patients, July 2003 -- http://www.townsendletter.com/July2003/LTRmartin0703.htm

  16. Digitoxin medication and cancer; case control and internal dose-response studies, Johan Haux et al, BMC Cancer 2001, 1:11 http://www.biomedcentral.com/1471-2407/1/11

  17. Digitoxin inhibits the growth of cancer cell lines at concentrations commonly found in cardiac patients, Miguel López-Lázaro et al, J. Nat. Prod,  October 18, 2005  --http://tinyurl.com/89862

  18. Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization, Joseph M. Langenhan, Jon S. Thorson et al. Proc Natl Acad. Sci 2005 Aug, 16 --http://www.pnas.org/cgi/content/abstract/0503270102v1

  19. Enhancement of radiotherapy by an endogenous cardiac glycoside. U.S. Provisional Patent Application Ser. No. 60/508,936, filed on Oct. 2, 2003 and published at Freshpatents.com on 26/05/05 -- http://www.tinyurl.com/c6zqb

  20. Methods for anti-tumor therapy. U.S. Patent No 6380167, filled on Feb. 02, 2000 and published at FreshPatents.com, April 2002 http://www.freepatentsonline.com/6380167.html

  21. Digitalis induced signaling by Na+/K+-ATPase in human breast cancer cells, Kometiani P et al. Mol Pharmacol 2005 March; 67(3): 929-36 --http://www.meduohio.edu/depts/pharm/pdf/929.pdf

  22. Na/K-ATPase, endogenous digitalis like compounds and cancer development - a hypothesis, Weidemann H. Front Biosci 2005 Sep 1;10:2165-76 -- http://tinyurl.com/9tbbe

  23. Sodium/potassium ATPase (Na(+), K(+) - ATPase) and ouabain/related cardiac glycosides: a new paradigm for development of anti-breast cancer drugs? Chen JQ, Contreras RG et al. Breast Cancer Res Treat 2005 Dec 2;1-15 -- http://tinyurl.com/d27lc

  24. Endogenous cardiac glycosides, a new class of steroid hormones, Wilhelm Schoner, Eur J Biochem. 268, 2440-2448, 2002. http://content.febsjournal.org/cgi/content/full/269/10/2440

  25. Digitalis: new actions for an old drug, Wasserstrom JA, Aistrup GL, Am J Physiol Heart Circ Physiol, 289: 1781-1793, 2005 -- http://tinyurl.com/m3cl8

  26. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Thaker PH, Sood AK et al, Nat Med 2006 Aug;12(8):939-44

  27. Norepinephrine Up-regulates the Expression of Vascular Endothelial Growth Factor, Matrix Metalloproteinase (MMP)-2, and MMP-9 in Nasopharyngeal Carcinoma Tumor Cells. Yang EV, Sood AK, Chen M, Li Y, Glaser R. et al, Cancer Res. 2006 Nov 1;66(21):10357- 10364.

  28. Contrasting effects of digitalis and dobutamine on baroreflex sympathetic control in normal humans, Schobel HP et al. Circulation V84, 1118-1129, 1991 http://circ.ahajournals.org/cgi/reprint/84/3/1118

  29. Mechanism of inhibition of catecholamine release from adrenal medulla by diphenylhydantoin and by low concentration of ouabain (10 (-10) M). Gutman Y, Boonyaviroj P. Naunyn Schmiedebergs Arch Pharmacol 1977 Feb;296(3):293-6. http://tinyurl.com/97a97

 

MEDIA