A New Understanding Of The Effect Of Vitamin "C" On Cancer Cells

Originally published November 6 2007
Written by Helmut Beierbeck

More than thirty years ago Linus Pauling and co-workers pioneered the therapeutic use of high doses of vitamin C (ascorbate) on terminal cancer patients, with promising results. Attempts by mainstream medicine to confirm Pauling’s results failed, largely because patients were given vitamin C orally, whereas Pauling’s group had gone the intravenous route. Intravenous administration achieves ascorbate concentrations that are orders of magnitude higher.

Neglected by mainstream medicine, intravenous vitamin C cancer treatment continued as an alternative medical practice, although the establishment of the U.S. National Cancer Institute Best Case Series prompted a recent report of three well-documented case studies of successful vitamin C cancer therapy(1).

There was another reason for the mainstream’s skepticism - the proposed mechanism of action of ascorbate appeared questionable. It was assumed that the antioxidant simply protected DNA from free radical damage, but this should protect the genetic material of healthy and cancerous tissues alike. The idea that ensuring DNA integrity should selectively favor healthy tissue over tumors seemed implausible.

Indeed, this interpretation turned out to be wrong. A group at Johns Hopkins Medical School reported recently that antioxidants inhibited three tumorigenic models in vivo, but that “[inhibition of a human B lymphoma model was] unassociated with genomic instability but was linked to diminished hypoxia-inducible factor (HIF) levels…”(2).

What the researchers found was that the differential effect of ascorbate on healthy tissue and cancer cells had nothing to do with the protection of DNA. Instead, ascorbate influenced the HIF-promoted transcription of selected genes. It was the suppression of the transcription of these genes by ascorbate that affected tumors and healthy tissues differently.

What is hypoxia-inducible factor (HIF)?

Hypoxia-inducible factor regulates the transcription of genes involved in angiogenesis, glucose uptake and metabolism, as well as other cellular functions. HIF is a protein that occurs in all mammalian cell types and that is activated when oxygen levels fall(3).

Normal oxygen levels deactivate HIF by hydroxylating key proline and asparagine residues. These hydroxylation reactions are catalyzed by enzymes containing divalent iron at the active site, and require molecular oxygen. Ascorbate is needed to keep iron in the ferrous (divalent) state for these HIF-deactivating enzymes to function properly. HIF deactivation in turn prevents or slows gene transcription of proteins promoting angiogenesis and glucose metabolism(3)

A growing tumor, unlike healthy tissue, needs new blood vessels (angiogenesis) to ensure a continuous supply of nutrients. And it had been known that HIF is often activated in solid tumors(3). Suppression of angiogenesis by deactivating hypoxia-inducible factor therefore selectively disadvantages tumor cells.

Efforts are already underway to create synthetic HIF suppressors to starve tumors, but megadoses of intravenously administered vitamin C seem to accomplish the task without known side effects. It should be interesting to see if this new understanding of the role of ascorbate in gene transcription is going to bring the treatment, or adjunct treatment, of cancer with IV-administered vitamin C into mainstream medicine.

Sources

1. Intravenously administered vitamin C as cancer therapy: three cases.

Sebastian J. Padayatta, Hugh D. Riordan, Stephen M. Hewitt, Arie Katz, L.John Hoffer and Mark Levine,

Can. Med. Assoc. J. 2006;174(7):937-942

2. HIF-Dependent Antitumorigenic Effect of Antioxidants In Vivo

Ping Gao, Huafeng Zhang, Ramani Dinavahi, Feng Li, Yan Xiang, Venu Raman, Zaver M. Bhujwalla, Dean W. Felsher, Linzhao Cheng, Jonathan Pevsner, Linda A. Lee, Gregg L. Semenza and Chi V. Dang

Cancer Cell 2007;12(3):230-238

3. Hypoxia-inducible factor as a physiological regulator.

Patrick H. Maxwell

Exp. Physiol. 2005;90(6):791-797

About the author

Helmut Beierbeck has a science background and a strong interest in all scientific aspects of health, nutrition, medicine, weight loss, or any other topic related to wellness. You can follow his ruminations on his blog http://healthcomments.info and leave comments on this or any other health-related topic.

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