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DOI: 10.1055/s-2007-968115
Karl F. Haug Verlag in MVS Medizinverlage Stuttgart GmbH & Co. KG
Vitamin C als Prodrug von H2O2: Möglichkeiten zur intravenösen Hochdosistherapie bei Krebserkrankungen?[*]
Publikationsverlauf
Publikationsdatum:
21. Juni 2007 (online)

Zusammenfassung
Die Rolle von Vitamin C (Ascorbinsäure) bei der Behandlung von Krebserkrankungen wird seit Jahren sehr kontrovers diskutiert und hat im Bereich der Schulmedizin nicht allzu viele Anhänger. Eine im September 2005 publizierte Arbeit einer renommierten Forschergruppe am NIH hat deshalb großes Aufsehen erregt, da hier, aufbauend auf Zellkulturversuchen, der Vorschlag gemacht wurde, hochdosiertes Vitamin C durch intravenöse Applikation bei der Therapie von Krebserkrankungen einzusetzen. Ascorbinsäure soll dabei über die Generierung von H2O2 wirksam sein. Diese Arbeit wird hier vorgestellt und besprochen und in Relation zu anderen möglichen Wirkungsmechanismen von Ascorbat gestellt.
Summary
Vitamin C as a prodrug of H2O2: Are there chances for an intravenous high-dose therapy of cancer?
The role of vitamin C (ascorbic acid) as an optional therapy of cancerous affections has been discussed for a couple of years. So far, this kind of treatment has not found many supporters. Based on cell cultures, a paper published in September 2005 by a group of reputed researchers at the NIH, came to the conclusion that intravenous application of high doses of vitamin C might have positive effects on cancer patients. It was suggested that ascorbic acid could cause generation of H2O2. We comment on essentials of this paper, indicating relationships to other work on the subject of potential mechanisms involved in connection with ascorbate.
Schlüsselwörter
Vitamin C - Ascorbinsäure - Krebstherapie - H2O2 - Wasserstoffperoxid - HIF - Warburg'sche Krebstheorie
Keywords
Vitamin C - ascorbic acid - cancer control - H2O2 - hydrogen peroxide - HIF - Warburg's cancer theory
01 Aktualisierter Nachdruck aus: Ernährung & Medizin (2006; 21: 120-124).
Literatur
- 01 Baader S L, Bruchelt G, Carmine T C, Lode H N, Rieth A G, Niethammer D. Ascorbic acid mediated iron release from cellular ferritin and its relation to DNA strand break formation in neuroblastoma cells. J Cancer Res Clin Oncol. 1994; 120 415-421
- 02 Barinaga M. Vitamin C gets a little respect. Science. 1991; 254 374-376
- 03 Berra E, Ginouvès A, Pouysségur J. The hypoxia-inducible-factor hydroxylases bring fresh air into hypoxia signalling. EMBO Rep.. 2006; 7 41-45
- 04 Bruchelt G, Schrauffstätter I, Niethammer D, Cochrane C G. Ascorbic acid enhances the effects of 6-hydroxydopamine and H2O2 on iron-dependent DNA strand breaks and related processes in the neuroblastoma cell line SK-N-SH. Cancer Res. 1991; 51 6066-6072
- 05 Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Reevaluation of prolongation of survival times in terminal human cancer. Proc Natl Acad Sci (USA). 1978; 75 4538-4542
-
06
Cameron E, Campell A.
Innovation vs. quality control: an ‚unpublishable’ clinical trial of supplemental ascorbate in incurable cancer.
1991.
36
185-189
- 07 Davies M B, Austin J, Partridge D A. Vitamin C: Its Chemistry and Biochemistry. Cambridge; Royal Society of Chemistry Paperbacks 1991
- 08 Esteban N A, Maxwell P H. HIF, a missing link between metabolism and cancer. Nature Med. 2005; 11 1047-1048
- 09 Garber K. Energy boost: The Warburg effect returns in a new theory of cancer. J Natl Cancer Inst. 2004; 96 1805-1806
- 10 Halliwell B, Gutteridge J M. Free Radicals in Biology and Medicine. 4th ed. Oxford; Science Publications 2007
- 11 Henson D E, Block G, Levine M. Ascorbic acid: Biologic functions and relation to cancer. J Natl Cancer Inst. 1991; 83 547-550
- 12 Knowles H J, Raval R R, Harris A L, Ratcliffe P J. Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells. Cancer Res. 2003; 63 1764-1768
- 13 Moertel C G, Fleming T R, Cregan E T. et al . High dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N Engl J Med. 1985; 312 137-141
- 14 Padayatty S J, Levine M. Reevaluation of ascorbate in cancer treatment: Emerging evidence, open minds and serendipity. J Am Coll Nutr. 2000; 19 423-425
- 15 Padayatty S J, Riordan H D, Hewitt S M, Katz A, Hoffer L J, Levine M. Intravenously administered vitamin C as cancer therapy: three cases. Can Med Assoc J. 2006; 174 937-942
- 16 Park S, Han S S, Park C H, Hahm E R. et al . L-Ascorbic acid induces apoptosis in acute myeloid leukemia cells via hydrogen peroxide-mediated mechanisms. Int J Biochem Cell Biol. 2004; 36 2180-2195
- 17 Park S, Lee J, Chang-Hwan Yeom. A proteomic approach to the identification of early molecular targets changed by ascorbic acid in NB4 human leukemia cells. J Cell Biochem. 2006; 99 1628-1641
- 18 Qi Chen, Espey M G, Krishna M C, Mitchell J B. et al . Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci (USA). 2005; 102 13604-13609
- 19 Qi Chen, Espey M G, Sun A Y, Je-Hyuk Lee, Krishna M C. et al . Ascorbate in pharmacological concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci (USA). 2007; 104 8749-8754
- 20 Schofield Ch J, Ratcliffe P J. Oxygen sensing by HIF hydroxylases. Natl Rev Mol Cell Biol. 2004; 5 343-353
- 21 Seifried H E, McDonald Sh S, Anderson D E, Greenwald P, Milner J A. The antioxidant conundrum in cancer. Cancer Res. 2003; 63 4295-4298
- 22 Semenza G L. HIF-1 and human disease: one highly involved factor. Genes Dev. 2000; 14 1983-1991
- 23 Semenza G L. Targeting HIF-1 for cancer therapy. Natl Rev Cancer. 2003; 3 721-732
- 24 Sestili P, Brandi G, Brambilla L, Cattabeni F, Cantoni O. Hydrogen peroxide mediates the killing of U937 tumor cells elicited by pharmacologically attainable concentrations of ascorbic acid: cell death prevention by extracellular catalase or catalase from cocultured erythrocytes or fibroblasts. J Pharmacol Exp Ther. 1996; 277 1719-1725
- 25 Warburg O, Posener K, Negelein E. Über den Stoffwechsel von Tumoren. Biochem Z. 1924; 152 319-344
- 26 Warburg O. On the origin of cancer cells. Science. 1956; 123 309-314
- 27 Wittes R E. Vitamin C and Cancer. N Engl J Med. 1985; 312 178-179
01 Aktualisierter Nachdruck aus: Ernährung & Medizin (2006; 21: 120-124).
Korrespondenzadresse
Prof. Dr. rer. nat. Gernot Bruchelt
Univ. Klinik für Kinder- und Jugendmedizin
Hoppe-Seyler-Str. 1
72076 Tübingen
eMail: gernot.bruchelt@med.uni-tuebingen.de