Vitamin C and cancer
Pharmacologic ascorbic acid
concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen
peroxide to tissues
Qi Chen *, , Michael Graham Espey ,
Murali C. Krishna , James B. Mitchell , Christopher P. Corpe *, Garry R. Buettner , Emily
Shacter and Mark Levine *, ¶
*Molecular and Clinical Nutrition
Section, National Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health, Bethesda, MD 20892; Radiation Biology Branch, National Cancer
Institute, National Institutes of Health, Bethesda, MD 20892; Free Radical and Radiation
Biology Program, University of Iowa, Iowa City, IA 52242-1101; and Laboratory of
Biochemistry, Center for Drug Evaluation and Research, Food and Drug Administration,
Bethesda, MD 20892
Human pharmacokinetics data
indicate that i.v. ascorbic acid (ascorbate) in pharmacologic concentrations could have an
unanticipated role in cancer treatment.
Our goals here were to test whether
ascorbate killed cancer cells selectively, and if so, to determine mechanisms, using
clinically relevant conditions. Cell death in 10 cancer and 4 normal cell types was
measured by using 1-h exposures. Normal cells were unaffected by 20 mM ascorbate, whereas
5 cancer lines had EC50 values of <4 mM, a concentration easily achievable i.v. Human
lymphoma cells were studied in detail because of their sensitivity to ascorbate (EC50 of
0.5 mM) and suitability for addressing mechanisms.
Extracellular but not intracellular
ascorbate mediated cell death, which occurred by apoptosis and pyknosis/necrosis. Cell
death was independent of metal chelators and absolutely dependent on H2O2 formation. Cell
death from H2O2 added to cells was identical to that found when H2O2 was generated by
ascorbate treatment. H2O2 generation was dependent on ascorbate concentration, incubation
time, and the presence of 0.5-10% serum, and displayed a linear relationship with
ascorbate radical formation. Although ascorbate addition to medium generated H2O2,
ascorbate addition to blood generated no detectable H2O2 and only trace detectable
ascorbate radical.
Taken together, these data indicate that
ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for
formation of H2O2, and that blood can be a delivery system of the pro-drug to tissues.
These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have
unexpected implications for treatment of infections where H2O2 may be beneficial.
The Dr. Rath Research Institute applauded
the findings of Dr. Mark Levine and colleagues at the U.S. National Institutes of Health,
which show that vitamin C has the potential to fight cancer when used in high dosages. The
study confirms earlier research findings published in numerous scientific cancer journals
by scientists from the Dr. Rath Research Institute.
The institute's research documents that
vitamin C, when used in combination with the amino acids L-lysine and L-proline and a
polyphenol fraction of green tea known as Epigallocatechin Gallate (EGCG), could not only
kill cancer cells, but limit tumor growth, its infiltration by blood vessels
(angiogenesis), and completely stop the invasion and spread of more than two dozen cancer
cell types. While the NIH study showed a 50 percent decrease in survival of cancer cells
exposed to high doses of vitamin C in five out of nine cancer cell types, the combination
of nutrients used by Rath's group was effective not only in eliminating cancer cells, but
in arresting cancer cell tissue invasion -- a hallmark of metastasis responsible for 90
percent of deaths from cancer. Today, there are no effective measures to stop cancer
metastasis.
Dr. Matthias Rath, founder of the Dr.
Rath Research Institute, said, "The use of lysine, an amino acid, in combination with
ascorbic vitamin C addresses common pathomechanisms of cancer, will lead to a breakthrough
in the control of many forms of cancer and other diseases." Dr. Rath first published
his concept of the natural control of cancer in the Journal of Applied Nutrition in 1992.
Research that confirmed Dr. Rath's
approach was publicized in an advertisement in USA Today on March 8, 2002. Further
research was presented at the 19th Annual Miami Breast Cancer Conference in February of
2002; at the American Association of Cancer Research Special Conference in Cancer Research
in South Carolina in October of 2002; at many other national and international
conferences; and in many publications. The most recent findings can be found at the Breast
Cancer Research Web site at http://breast-cancer-research.com/content/7/3/R291.
"By using nutrient synergy and
defining correct biological targets, we could achieve superior physiological effects,
which is not possible with a single nutrient therapy, even if applied at extreme
doses," said Dr. Aleksandra Niedzwiecki, director of research at the institute.
The Dr. Rath Research Institute is
calling for a radical change in the treatment of cancer, one that takes advantage of new
natural approaches. Conventional approaches, such as chemotherapy and radiation, have been
unsuccessful in reducing the high mortality rate of the disease, have contributed only to
the accelerated cost of health care, and led to the development of new diseases that
result from the side effects of these treatments.
The Dr. Rath Research Institute offers
innovative, safe, effective, and natural solutions to cancer. To learn more, visit www.drrathresearch.org.
Source: Dr. Rath Education
Services USA, BV
Tsao, Constance; Dunham, Wolcott;
and Leung; Ping. Growth control of human colon tumor xenografts by ascorbic acid, copper,
and iron. The Cancer Journal, vol. 8, pp. 157-163 (1995)
The authors of this study previously reported that a combination of ascorbic acid and
copper sulfate inhibited the growth of small fragments of human mammary or lung tumors
explanted in mice. Fragments of the human tumors were implanted under the renal capsule of
mice and measured after six days of treatment. This method allows for evaluation of the
immune-independent anti-cancer effect of the test agents, since the immune system does not
respond quickly to the xenograft. In another set of experiments reported in this paper,
Drs. Tsao, Dunham, and Leung showed that the growth of human colon adenocarcinoma explants
in mice was also inhibited by a combination of large amounts of ascorbic acid in the diet
and copper or iron ions supplied in the drinking water. The administration of metal ions
without vitamin C increased tumor growth, whereas vitamin C alone suppressed tumor growth
in some animals. The combination of ascorbic acid and metal ions proved much more
effective than the vitamin alone, indicating that the anti-cancer effect was due to
products formed by the oxidation of vitamin C, which is catalyzed by the metal ions,
rather than to its vitamin activity.
Tsao, Constance and Young, May.
Molecular structure-dependent cytotoxic effect of ascorbate derivatives. In Vitro Cellular
and Developmental Biology, volume 31, pp. 87-90 (1995)
In this letter, Dr. Tsao and Ms. Young suggest that the anticancer, cytotoxic effect of
ascorbate derivatives and degradation products are dependent on the chemical structure,
rather than the vitamin activity, of ascorbic acid. They compared the cytotoxic effect of
derivatives of vitamin C formed by oxidation, other degradation products of vitamin C, and
its isomers on mouse leukemia cells. Their results suggest that the cytotoxic moiety
resides in the enediol lactone ring structure of the molecules. This line of research may
suggest novel therapeutics for cancer treatment.
Ascorbid Acid can kill cancer
cells
Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action
as a pro-drug to deliver hydrogen peroxide to tissues
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