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, we have noticed 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 us to verify the cancer mortality rate for patients in similar medical condition and age, presented in other studies. Also, we have made a search at Medline, finding out 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. Weidemann found that the majority (73.6%) of breast cancer patients (n=84) expressed lower plasma DLC concentrations (b50 pmol/L) than the control group (150±30 pmol/L).
* 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 (October 05, 2008):
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) Lactic acid, cardiac glycosides and cancer
German Otto Warburg, PH.D, Nobel laureate in medicine in 1931, first discovered that cancer cells have a fundamentally different energy metabolism compared to healthy cells. The essence of his Nobel thesis was the malignant tumors frequently exhibit an increase in "aerobic glycolysis" a process whereby glucose is used by cancer cells as a fuel with lactic acid as an aerobic byproduct -- compared to normal tissues. The large amount of lactic acid produced by this fermentation of glucose from the cancer cells is then transported to the liver (30). In 1966 was discovered by Manfred von Ardenne that cancer cells, owing to their fermentation, are more acid inside and on their surface - than normal cells (31). It is interesting to note that cardiac glycosides can re-elevate a lowered pH by stopping the over production of lactic acid (32). Also interesting is that studies have suggested a causal relationship between noradrenaline/adrenaline and concentrations of lactic acid (33).
3) Clinical studies in
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
c) A pilot phase II study of digitoxin for Androgen-Independent Prostate Cancer (AIPC) March 2007, J Haux et al. http://www.fou.nu/is/sverige/document/2151
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